BTS guidelines

British Thoracic Society guidelines for the Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from management of community acquired pneumonia in adults: update 2009 W S Lim, S V Baudouin, R C George, A T Hill, C Jamieson, I Le Jeune, J T Macfarlane, R C Read, H J Roberts, M L Levy, M Wani, M A Woodhead, Pneumonia Guidelines Committee of the BTS Standards of Care Committee c Full search strategies for each SYNOPSIS OF RECOMMENDATIONS 6. It is the responsibility of the hospital team to database are published online A summary of the initial management of patients arrange the follow-up plan with the patient only at http://thorax.bmj.com/ admitted to hospital with suspected community and the general practitioner for those patients content/vol64/issueSupplIII acquired pneumonia (CAP) is presented in fig 8. admitted to hospital. [D] Tables 4 and 5, respectively, summarise (1) the relevant microbiological investigations and (2) Correspondence to: What general investigations should be done in the Dr W S Lim, Respiratory empirical antibiotic choices recommended in Medicine, Nottingham University patients with CAP. community? Hospitals, David Evans Building, 7. General investigations are not necessary for Hucknall Road, Nottingham NG5 the majority of patients with CAP who are 1PB, UK; [email protected] Investigations (Section 5) When should a chest radiograph be performed in the managed in the community. [C] Pulse oxi- meters allow for simple assessment of oxyge- Received 11 June 2009 community? Accepted 6 July 2009 nation. General practitioners, particularly 1. It is not necessary to perform a chest radio- those working in out-of-hours and emergency graph in patients with suspected CAP unless: assessment centres, should consider their use. – The diagnosis is in doubt and a chest radio- [D] graph will help in a differential diagnosis and 8. Pulse oximetry should be available in all management of the acute illness. [D] locations where emergency oxygen is used. – Progress following treatment for suspected [D] CAP is not satisfactory at review. [D] – The patient is considered at risk of under- lying lung pathology such as lung cancer. [D] What general investigations should be done in a patient admitted to hospital? http://thorax.bmj.com/ When should a chest radiograph be performed in 9. All patients should have the following tests hospital? performed on admission: 2. All patients admitted to hospital with suspected – Oxygenation saturations and, where neces- CAP should have a chest radiograph performed sary, arterial blood gases in accordance with as soon as possible to confirm or refute the the BTS guideline for emergency oxygen use diagnosis. [D] The objective of any service in adult patients. [B+] should be for the chest radiograph to be – Chest radiograph to allow accurate diagnosis.

performed in time for antibiotics to be admi- [B+] on October 1, 2021 by guest. Protected copyright. nistered within 4 h of presentation to hospital – Urea and electrolytes to inform severity should the diagnosis of CAP be confirmed. assessment. [B+] – C-reactive protein to aid diagnosis and as a When should the chest radiograph be repeated during baseline measure. [B+] recovery? – Full blood count. [B2] 3. The chest radiograph need not be repeated – Liver function tests. [D] prior to hospital discharge in those who have made a satisfactory clinical recovery from CAP. [D] Why are microbiological investigations performed? 4. A chest radiograph should be arranged after 10. Microbiological tests should be performed on about 6 weeks for all those patients who have all patients with moderate and high severity persistence of symptoms or physical signs or CAP, the extent of investigation in these who are at higher risk of underlying malig- patients being guided by severity. [D] nancy (especially smokers and those aged 11. For patients with low severity CAP the extent .50 years) whether or not they have been of microbiological investigations should be admitted to hospital. [D] guided by clinical factors (age, comorbid 5. Further investigations which may include illness, severity indicators), epidemiological bronchoscopy should be considered in factors and prior antibiotic therapy. [A2] patients with persisting signs, symptoms 12. Where there is clear microbiological evidence and radiological abnormalities at around of a specific pathogen, empirical anti- 6 weeks after completing treatment. [D] biotics should be changed to the appropriate

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii1 BTS guidelines

pathogen-focused agent unless there are legitimate con- Other tests for Streptococcus pneumoniae Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from cerns about dual pathogen infection. [D] 25. Pneumococcal urine antigen tests should be performed for all patients with moderate or high severity CAP. [A2] What microbiological investigations should be performed in the 26. A rapid testing and reporting service for pneumococcal community? urine antigen should be available to all hospitals admitting patients with CAP. [B+] 13. For patients managed in the community, microbiological investigations are not recommended routinely. [D] Tests for Legionnaires’ disease 14. Examination of sputum should be considered for patients who do not respond to empirical antibiotic therapy. [D] 27. Investigations for legionella pneumonia are recommended for all patients with high severity CAP, for other patients 15. Examination of sputum for Mycobacterium tuberculosis with specific risk factors and for all patients with CAP should be considered for patients with a persistent during outbreaks. [D] productive cough, especially if malaise, weight loss or night sweats, or risk factors for tuberculosis (eg, ethnic 28. Legionella urine antigen tests should be performed for all origin, social deprivation, elderly) are present. [D] patients with high severity CAP. [B+] 16. Urine antigen investigations, PCR of upper (eg, nose and 29. A rapid testing and reporting service for legionella urine throat swabs) or lower (eg, sputum) respiratory tract antigen should be available to all hospitals admitting + samples or serological investigations may be considered patients with CAP. [B ] during outbreaks (eg, Legionnaires’ disease) or epidemic 30. As the culture of legionella is very important for clinical mycoplasma years, or when there is a particular clinical or reasons and source identification, specimens of respiratory epidemiological reason. [D] secretions, including sputum, should be sent from patients with high severity CAP or where Legionnaires’ disease is suspected on epidemiological or clinical grounds. [D] The What microbiological investigations should be performed in hospital? clinician should specifically request legionella culture on Blood cultures laboratory request forms. 17. Blood cultures are recommended for all patients with 31. Legionella cultures should be routinely performed on invasive respiratory samples (eg, obtained by broncho- moderate and high severity CAP, preferably before anti- scopy) from patients with CAP. [D] biotic therapy is commenced. [D] 32. For all patients who are legionella urine antigen positive, 18. If a diagnosis of CAP has been definitely confirmed and a clinicians should send respiratory specimens such as patient has low severity pneumonia with no comorbid sputum and request legionella culture [D]. This is to aid disease, blood cultures may be omitted. [A2] outbreak and source investigation with the aim of preventing further cases. Sputum cultures

19. Sputum samples should be sent for culture and sensitivity Tests for Mycoplasma pneumoniae http://thorax.bmj.com/ tests from patients with CAP of moderate severity who are 33. Where available, PCR of respiratory tract samples such as able to expectorate purulent samples and have not received sputum should be the method of choice for the diagnosis of prior antibiotic therapy. Specimens should be transported mycoplasma pneumonia. [D] rapidly to the laboratory. [A2] 34. In the absence of a sputum or lower respiratory tract 20. Culture of sputum or other lower respiratory tract samples sample, and where mycoplasma pneumonia is suspected should also be performed for all patients with high severity on clinical and epidemiological grounds, a throat swab for CAP or those who fail to improve. [A2] Mycoplasma pneumoniae PCR is recommended. [D] 21. Sputum cultures for Legionella spp should always be 35. Serology with the complement fixation test and a range of on October 1, 2021 by guest. Protected copyright. attempted for patients who are legionella urine antigen other assays is widely available, although considerable positive in order to provide isolates for epidemiological caution is required in interpretation of results. [C] typing and comparison with isolates from putative environmental sources. [D] Tests for Chlamydophila species 36. Chlamydophila antigen and/or PCR detection tests should Sputum Gram stain be available for invasive respiratory samples from patients with high severity CAP or where there is a strong suspicion 22. Clinicians should establish with local laboratories the of psittacosis. [D] availability or otherwise of sputum Gram stain. Where this is available, laboratories should offer a reliable Gram stain 37. The complement fixation test remains the most suitable for patients with high severity CAP or complications as and practical serological assay for routine diagnosis of 2 occasionally this can give an immediate indicator of the respiratory Chlamydophila infections. [B ] There is no likely pathogen. Routine performance or reporting of currently available serological test that can reliably detect sputum Gram stain on all patients is unnecessary but acute infection due to C pneumoniae. can aid the laboratory interpretations of culture results. [B2] PCR and serological tests for other respiratory pathogens 23. Samples from patients already in receipt of antimicrobials 38. Where PCR for respiratory viruses and atypical pathogens are rarely helpful in establishing a diagnosis. [B2] is readily available or obtainable locally, this is preferred to 24. Laboratories performing sputum Gram stains should serological investigations. [D] adhere to strict and locally agreed criteria for interpretation 39. Where available, paired serology tests can be considered for and reporting of results. [B+] patients with high severity CAP where no particular iii2 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

microbiological diagnosis has been made by other means 54. All patients deemed at high risk of death on admission to Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from (eg, culture, urine antigen, PCR) and who fail to improve, hospital should be reviewed medically at least 12-hourly and/or where there are particular epidemiological risk until shown to be improving. [D] factors. [D] The date of onset of symptoms should be clearly indicated on all serological request forms. [D] General management (Section 7) 40. Serological tests may be extended to all patients admitted General management strategy for patients treated in the community to hospital with CAP during outbreaks and when needed for the purposes of surveillance. The criteria for performing 55. Patients with suspected CAP should be advised to rest, to serology tests in these circumstances should be agreed drink plenty of fluids and not to smoke. [D] locally between clinicians, laboratories and public health. 56. Pleuritic pain should be relieved using simple analgesia [D] such as paracetamol. [D] 57. The need for hospital referral should be assessed using the Severity assessment (Section 6) criteria recommended in section 6. [C] What severity assessment strategy is recommended? 58. Pulse oximetry, with appropriate training, should be 41. Clinical judgement is essential in disease severity assess- available to general practitioners and others responsible for ment. [D] the assessment of patients in the out-of-hours setting for the assessment of severity and oxygen requirement in patients 42. The stability of any comorbid illness and a patient’s social with CAP and other acute respiratory illnesses. [D] circumstances should be considered when assessing disease severity. [D] Review policy for patients managed in the community Severity assessment of CAP in patients seen in the community 59. Review of patients in the community with CAP is 43. For all patients, clinical judgement supported by the recommended after 48 h or earlier if clinically indicated. CRB65 score should be applied when deciding whether Disease severity assessment should form part of the clinical to treat at home or refer to hospital. [D] review. [D] 44. Patients who have a CRB65 score of 0 are at low risk of 60. Those who fail to improve after 48 h of treatment should death and do not normally require hospitalisation for be considered for hospital admission or chest radiography. clinical reasons. [B+] [D] 45. Patients who have a CRB65 score of 1 or 2 are at increased risk of death, particularly with a score of 2, and hospital General management strategy for patients treated in hospital referral and assessment should be considered. [B+] 61. All patients should receive appropriate oxygen therapy 46. Patients who have a CRB65 score of 3 or more are at high with monitoring of oxygen saturations and inspired risk of death and require urgent hospital admission. [B+] oxygen concentration with the aim to maintain arterial 47. When deciding on home treatment, the patient’s social oxygen tension (PaO2)at>8 kPa and oxygen saturation circumstances and wishes must be taken into account in (SpO2) 94–98%. High concentrations of oxygen can safely http://thorax.bmj.com/ all instances. [D] be given in patients who are not at risk of hypercapnic respiratory failure. [D] Severity assessment of CAP in patients seen in hospital 62. Oxygen therapy in patients at risk of hypercapnic respiratory failure complicated by ventilatory failure 48. For all patients, the CURB65 score should be interpreted in should be guided by repeated arterial blood gas measure- conjunction with clinical judgement. [D] ments. [C] 49. Patients who have a CURB65 score of 3 or more are at high 63. Patients should be assessed for volume depletion and may risk of death. These patients should be reviewed by a require intravenous fluids. [C] senior physician at the earliest opportunity to refine on October 1, 2021 by guest. Protected copyright. 64. Prophylaxis of venous thromboembolism with low mole- disease severity assessment and should usually be managed as having high severity pneumonia. Patients with CURB65 cular weight heparins should be considered for all patients who are not fully mobile. [A+] scores of 4 and 5 should be assessed with specific consideration to the need for transfer to a critical care 65. Nutritional support should be given in prolonged illness. unit (high dependency unit or intensive care unit). [B+] [C] 50. Patients who have a CURB65 score of 2 are at moderate 66. Medical condition permitting, patients admitted to hospi- risk of death. They should be considered for short-stay tal with uncomplicated CAP should sit out of bed for at inpatient treatment or hospital-supervised outpatient least 20 min within the first 24 h and mobility should be treatment. [B+] increased each subsequent day of hospitalisation. [A2] 51. Patients who have a CURB65 score of 0 or 1 are at low risk 67. Patients admitted with uncomplicated pneumonia should of death. These patients may be suitable for treatment at not be treated with traditional airway clearance techniques home. [B+] routinely. [B+] 52. When deciding on home treatment, the patient’s social 68. Patients should be offered advice regarding expectoration if circumstances and wishes must be taken into account in there is sputum present. [D] all instances. [D] 69. Airway clearance techniques should be considered if the patient has sputum and difficulty with expectoration or in Reviewing severity status after initial assessment the event of a pre-existing lung condition. [D] 53. Regular assessment of disease severity is recommended for all patients following hospital admission. The ‘‘post take’’ Monitoring in hospital round by a senior doctor and the medical team provides 70. Temperature, respiratory rate, pulse, blood pressure, one early opportunity for this review. [D] mental status, oxygen saturation and inspired oxygen

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii3 BTS guidelines

concentration should be monitored and recorded initially 85. For those patients referred to hospital with suspected high Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from at least twice daily and more frequently in those with severity CAP and where there are likely to be delays of over severe pneumonia or requiring regular oxygen therapy. [C] 6 h in the patient being admitted and treated in hospital, 71. C-reactive protein should be remeasured and a chest general practitioners should consider administering anti- radiograph repeated in patients who are not progressing biotics in the community. [D] satisfactorily after 3 days of treatment. [B+] 72. Patients should be reviewed within 24 h of planned discharge When should the first dose of antibiotics be given to patients home, and those suitable for discharge should not have more admitted to hospital? than one of the following characteristics present (unless they 86. A diagnosis of CAP should be confirmed by chest radio- represent the usual baseline status for that patient): graphy before the commencement of antibiotics in the temperature .37.8uC, heart rate .100/min, respiratory rate majority of patients. Selected patients with life-threaten- .24/min, systolic blood pressure ,90 mm Hg, oxygen ing disease should be treated based on a presumptive clinical saturation ,90%, inability to maintain oral intake and diagnosis of CAP. In such instances, an immediate chest abnormal mental status. [B+] radiograph to confirm the diagnosis or to indicate an alternative diagnosis is indicated. [D] Critical care management of CAP 87. All patients should receive antibiotics as soon as the 73. Patients with CAP admitted to ICUs should be managed diagnosis of CAP is confirmed. [D] This should be before by specialists with appropriate training in intensive care they leave the initial assessment area (emergency depart- working in close collaboration with specialists in respira- ment or acute medical unit). The objective for any service tory medicine. [D] should be to confirm a diagnosis of pneumonia with chest 74. Neither non-invasive ventilation (NIV) nor continuous radiography and initiate antibiotic therapy for the majority positive airways pressure (CPAP) support is routinely of patients with CAP within 4 h of presentation to indicated in the management of patients with respiratory hospital. [B2] failure due to CAP. [A2] 75. If a trial of non-invasive support is considered indicated in Empirical antibiotic choice for adults hospitalised with low severity CAP, it must only be conducted in a critical care area CAP where immediate expertise is available to enable a rapid 88. Most patients with low severity CAP can be adequately transition to invasive ventilation. [D] treated with oral antibiotics. [C] 76. Steroids are not recommended in the routine treatment of 89. Oral therapy with amoxicillin is preferred for patients with + high severity CAP. [A ] low severity CAP who require hospital admission for other 77. Granulocyte colony stimulating factor is not routinely reasons such as unstable comorbid illnesses or social needs. recommended as an adjunct to antibiotics. [A+] [D] 90. When oral therapy is contraindicated, recommended Follow-up arrangements parenteral choices include intravenous amoxicillin or http://thorax.bmj.com/ 78. Clinical review should be arranged for all patients at benzylpenicillin, or clarithromycin. [D] around 6 weeks, either with their general practitioner or in a hospital clinic. [D] Empirical antibiotic choice for adults hospitalised with moderate 79. At discharge or at follow-up, patients should be offered severity CAP access to information about CAP such as a patient 91. Most patients with moderate severity CAP can be information leaflet. [D] adequately treated with oral antibiotics. [C] 80. It is the responsibility of the hospital team to arrange the 92. Oral therapy with amoxicillin and a macrolide is preferred follow-up plan with the patient and the general practi- for patients with moderate severity CAP who require on October 1, 2021 by guest. Protected copyright. tioner. [D] hospital admission. [D] – Monotherapy with a macrolide may be suitable for Antibiotic management (Section 8) patients who have failed to respond to an adequate course Empirical antibiotic choice for adults treated in the community of amoxicillin before admission. Deciding on the adequacy of prior therapy is difficult and is a matter of individual 81. For patients treated in the community, amoxicillin clinical judgement. It is therefore recommended that remains the preferred agent at a dose of 500 mg three combination antibiotic therapy is the preferred choice in times daily. [A+] this situation and that the decision to adopt monotherapy 82. Either doxycycline [D] or clarithromycin [A2] are appro- is reviewed on the ‘‘post take’’ round within the first 24 h priate as an alternative choice, and for those patients who of admission. [D] are hypersensitive to penicillins. 93. When oral therapy is contraindicated, the preferred 83. Those with features of moderate or high severity infection parenteral choices include intravenous amoxicillin or should be admitted urgently to hospital. [C] benzylpenicillin, together with clarithromycin. [D] 94. For those intolerant of penicillins or macrolides, oral Should general practitioners administer antibiotics prior to hospital doxycyline is the main alternative agent. Oral levofloxacin transfer? and oral moxifloxacin are other alternative choices. [D] 84. For those patients referred to hospital with suspected CAP 95. When oral therapy is contraindicated in those intolerant of and where the illness is considered to be life-threatening, penicillins, recommended parenteral choices include levo- general practitioners should administer antibiotics in the floxacin monotherapy or a second-generation (eg, cefur- community. [D] Penicillin G 1.2 g intravenously or oxime) or third-generation (eg, cefotaxime or ceftriaxone) amoxicillin 1 g orally are the preferred agents. cephalosporin together with clarithromycin. [D] iii4 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

Empirical antibiotic choice for adults hospitalised with high severity fluoroquinolone with effective pneumococcal cover are Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from CAP alternative options. [D] 96. Patients with high severity pneumonia should be treated 110. Adding a fluoroquinolone is an option for those with high immediately after diagnosis with parenteral antibiotics. severity pneumonia not responding to a b-lactam/macro- [B2] lide combination antibiotic regimen. [D] 97. An intravenous combination of a broad-spectrum b- lactamase stable antibiotic such as co-amoxiclav together Avoiding inappropriate antibiotic prescribing with a macrolide such as clarithromycin is preferred. [C] 111. The diagnosis of CAP and the decision to start antibiotics 98. In patients allergic to penicillin, a second-generation (eg, should be reviewed by a senior clinician at the earliest cefuroxime) or third-generation (eg, cefotaxime or cef- opportunity. There should be no barrier to discontinuing triaxone) cephalosporin can be used instead of co- antibiotics if they are not indicated. [D] amoxiclav, together with clarithromycin. [C] 112. The indication for antibiotics should be clearly documen- ted in the medical notes. [D] When should the intravenous or the oral route be chosen? 113. The need for intravenous antibiotics should be reviewed 99. The oral route is recommended in those with low and daily. [D] moderate severity CAP admitted to hospital provided there 114. De-escalation of therapy, including the switch from are no contraindications to oral therapy. [B+] intravenous to oral antibiotics, should be considered as soon as is appropriate, taking into account response to When should the intravenous route be changed to oral? treatment and changing illness severity. [D] 100. Patients treated initially with parenteral antibiotics should be 115. Strong consideration should be given to narrowing the transferred to an oral regimen as soon as clinical improve- spectrum of antibiotic therapy when specific pathogens are ment occurs and the temperature has been normal for 24 h, identified or when the patient’s condition improves. [D] providing there is no contraindication to the oral route. 116. Where appropriate, stop dates should be specified for Pointers to clinical improvement are given in box 4. [B+] antibiotic prescriptions. [D] 101. The choice of route of administration should be reviewed initially on the ‘‘post take’’ round and then daily. [D] Optimum antibiotic choices when specific pathogens have been 102. Ward pharmacists could play an important role in identified facilitating this review by highlighting prescription charts 117. If a specific pathogen has been identified, the antibiotic where parenteral antibiotic therapy continues. [D] recommendations are as summarised in table 6. [C]

Which oral antibiotics are recommended on completion of intravenous therapy? Specific issues regarding the management of Legionnaires’ disease 103. The antibiotic choices for the switch from intravenous to 118. As soon as a diagnosis of legionella pneumonia has been oral are straightforward where there are effective and made, the clinician should liaise with the clinical micro- http://thorax.bmj.com/ equivalent oral and parenteral formulations. [C] biologist to confirm that the local Health Protection Unit 104. In the case of parenteral cephalosporins, the oral switch to has been informed. The Health Protection Unit is co-amoxiclav 625 mg three times daily is recommended responsible for promptly investigating the potential rather than to oral cephalosporins. [D] sources of infection. [D] 105. For those treated with benzylpenicillin + levofloxacin, oral 119. The clinician should assist, where appropriate, in the levofloxacin with or without oral amoxicillin 500 mg–1.0 g gathering of clinical and epidemiological information from three times daily is recommended. [D] the patient and their relatives to aid the source investiga- tion. [D] on October 1, 2021 by guest. Protected copyright. How long should antibiotics be given for? 120. Sputum or respiratory secretions should be sent off specifically for legionella culture in proven cases, even 106. For patients managed in the community and for most after appropriate antibiotics have started. [D] patients admitted to hospital with low or moderate 121. For low and moderate severity community acquired severity and uncomplicated pneumonia, 7 days of appro- legionella pneumonia, an oral fluoroquinolone is recom- priate antibiotics is recommended. [C] mended. In the unusual case when this is not possible due 107. For those with high severity microbiologically-undefined to patient intolerance, a macrolide is an alternative. [D] pneumonia, 7–10 days of treatment is proposed. This may Antibiotics are not required for the non-pneumonic self- need to be extended to 14 or 21 days according to clinical limiting form of legionellosis—pontiac fever. [D] judgement; for example, where Staphylococcus aureus or 122. For the management of high severity or life-threatening Gram-negative enteric bacilli pneumonia is suspected or legionella pneumonia, a fluoroquinolone is recommended. confirmed. [C] For the first few days this can be combined with a macrolide (azithromycin is an option in countries where it Failure of initial empirical therapy is used for pneumonia) or rifampicin as an alternative. [D] 108. When a change in empirical antibiotic therapy is con- Clinicians should be alert to the potential small risk of sidered necessary, a macrolide could be substituted for or cardiac electrophysiological abnormalities with quinolone- added to the treatment for those with low severity macrolide combinations. pneumonia treated with amoxicillin monotherapy in the 123. Duration of therapy should be as for microbiologically- community or in hospital. [D] undefined CAP (for those with low to moderate severity 109. For those with moderate severity pneumonia in hospital pneumonia, 7 days treatment is proposed; for those on combination therapy, changing to doxycycline or a with high severity pneumonia, 7–10 days treatment is

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii5 BTS guidelines

proposed—this may need to be extended to 14 or 21 days) vaccine (23-PPV) at convalescence in line with the Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from and should be guided by clinical judgement. [D] Department of Health guidelines. [C]

Smoking cessation Specific issues regarding Panton-Valentine Leukocidin-producing 137. Smoking cessation advice should be offered to all patients Staphylococcus aureus (PVL-SA) with CAP who are current smokers according to smoking 124. PVL-SA infection is a rare cause of high severity cessation guidelines issued by the Health Education pneumonia and can be associated with rapid lung Authority. [B+] cavitation and multiorgan failure. Such patients should be considered for critical care admission. [D] SECTION 1 INTRODUCTION 125. If PVL-SA necrotising pneumonia is strongly suspected or 1.1 Scope of these guidelines confirmed, clinicians should liaise urgently with the c These guidelines refer to the management of adults with microbiology department in relation to further antibiotic community acquired pneumonia (CAP) of all ages in the management and consider referral to the respiratory community or in hospital. They have been developed to medicine department for clinical management advice. [D] apply to the UK healthcare system and population. They 126. Current recommendations for the antibiotic management might equally be applicable to any other countries which of strongly suspected necrotising pneumonia include the operate similar healthcare services (figs 1 and 2). addition of a combination of intravenous linezolid 600 mg c They are NOT aimed at patients with known predisposing twice daily, intravenous clindamycin 1.2 g four times a day conditions such as cancer or immunosuppression admitted and intravenous rifampicin 600 mg twice daily to the with pneumonia to specialist units such as oncology, initial empirical antibiotic regimen. As soon as PVL-SA haematology, palliative care, infectious diseases units or infection is either confirmed or excluded, antibiotic AIDS units. therapy should be narrowed accordingly. [D] c They do NOT apply to the much larger group of adults with non-pneumonic lower respiratory tract infection, including Complications and failure to improve (Section 9) illnesses labelled as acute bronchitis, acute exacerbations of Failure to improve in hospital chronic obstructive pulmonary disease or ‘‘chest infections’’. 127. For patients who fail to improve as expected, there should be a careful review by an experienced clinician of the 1.2 Introduction clinical history, examination, prescription chart and results The British Thoracic Society (BTS) guidelines for the manage- of all available investigation results. [D] ment of Community Acquired Pneumonia (CAP) in Adults were 128. Further investigations including a repeat chest radiograph, published in December 20011 and superseded guidelines C-reactive protein and white cell count and further published in 1993. A web-based update of the 2001 guidelines specimens for microbiological testing should be considered was published in 2004.2 The 2004 guidelines assessed relevant in the light of any new information after the clinical

evidence published up to August 2003. http://thorax.bmj.com/ review. [D] This update represents a further assessment of published or 129. Referral to a respiratory physician should be considered. available evidence from August 2003 to August 2008. An [D] identical search strategy, assessment of relevance and appraisal of articles and grading system was used (see Section 1.8 and Common complications of CAP Appendices 1–4). c This document incorporates material from the 2001 and 130. Early thoracocentesis is indicated for all patients with a 2004 guidelines and supersedes the previous guideline parapneumonic effusion. [D] documents. 131. Those found to have an empyema or clear pleural fluid on October 1, 2021 by guest. Protected copyright. with pH ,7.2 should have early and effective pleural fluid drainage. [C] 1.3 Definitions 1.3.1 Defining community acquired pneumonia (CAP) 132. The British Thoracic Society guidelines for the manage- ment of pleural infection should be followed. [D] The diagnosis in hospital will be made with the benefit of a chest radiograph. In the community, the recognition and 133. Less usual respiratory pathogens including anaerobes, S definition of CAP by general practitioners in the UK, without aureus, Gram-negative enteric bacilli and S milleri should be considered in the presence of lung abscess. [D] the benefit of investigations or radiology, poses greater challenges and the diagnosis will often be based only on clinical 134. Prolonged antibiotic therapy of up to 6 weeks depending features. on clinical response and occasionally surgical drainage should be considered. [D] 1.3.1.1 Defining CAP in a community setting The clinical definition of CAP that has been used in community Prevention and vaccination (Section 10) studies has varied widely but has generally included a complex Influenza and pneumococcal vaccination of symptoms and signs both from the respiratory tract and 135. Department of Health guidelines in relation to influenza regarding the general health of the patient. Features such as and pneumococcal immunisation of at-risk individuals fever (.38uC), pleural pain, dyspnoea and tachypnoea and signs should be followed. [C] on physical examination of the chest (particularly when new 136. All patients aged .65 years or at risk of invasive and localising) seem most useful when compared with the gold pneumococcal disease who are admitted with CAP and standard of radiological diagnosis of CAP.3 [II] See Section 5.1 for who have not previously received pneumococcal vaccine a fuller discussion pertaining to the clinical diagnosis of CAP should receive 23-valent pneumococcal polysaccharide managed in the community. iii6 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

Figure 1 Synopsis of the management Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from of adult patients seen in the community with suspected community acquired pneumonia, with cross reference to relevant sections in the document text. http://thorax.bmj.com/ on October 1, 2021 by guest. Protected copyright.

For the purposes of these guidelines, CAP in the community combination of symptoms, signs and radiological features. The has been defined as: BTS study of CAP used a definition which included: an acute c Symptoms of an acute lower respiratory tract illness (cough illness with radiographic shadowing which was at least and at least one other lower respiratory tract symptom). segmental or present in more than one lobe and was not c New focal chest signs on examination. known to be previously present or due to other causes.6 Like c At least one systemic feature (either a symptom complex of most studies, cases were excluded if pneumonia occurred distal sweating, fevers, shivers, aches and pains and/or tempera- to a known carcinoma or foreign body. ture of 38uC or more). For the purposes of these guidelines, CAP in hospital has been c No other explanation for the illness, which is treated as CAP defined as: with antibiotics. c Symptoms and signs consistent with an acute lower respiratory tract infection associated with new radiographic 1.3.1.2 Definition of CAP in patients admitted to hospital (when a shadowing for which there is no other explanation (eg, not chest radiograph is available) pulmonary oedema or infarction). Studies of CAP from different countries have used very different c The illness is the primary reason for hospital admission and definitions and inclusion criteria;3–5 most have required a is managed as pneumonia.

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii7 BTS guidelines

Figure 2 Synopsis of the management Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from of adult patients seen in hospital with suspected community acquired pneumonia, with cross reference to relevant sections in the document text. http://thorax.bmj.com/ on October 1, 2021 by guest. Protected copyright.

1.3.2 Defining the terms ‘‘atypical pneumonia’’ and ‘‘atypical Legionella spp, although sharing some of these characteristics, pathogens’’ are not considered to be an ‘‘atypical pathogen’’ for the purpose The term ‘‘atypical pneumonia’’ has outgrown its historical of this document as there are different species and these can be usefulness and we do not recommend its continued use as it acquired both in the community and hospital environment. implies (incorrectly) a distinctive clinical pattern (see Section 4.2). 1.3.3 Defining the term ‘‘elderly’’ For the purposes of these guidelines, the term ‘‘atypical There is no agreed age cut-off to define the term ‘‘elderly’’. pathogens’’ is used to define infections caused by: When referring to published research, wherever possible we c Mycoplasma pneumoniae; define the age limits used in the relevant studies. c Chlamydophila pneumoniae; c Chlamydophila psittaci; and 1.4 What is the target end user audience? c Coxiella burnetii. We want these guidelines to be of value to: These pathogens are characterised by being difficult to c Hospital-based medical and other staff involved with diagnose early in the illness and are sensitive to antibiotics managing adult patients with CAP. other than b-lactams such as macrolides, tetracyclines or c General practitioners. fluoroquinolones which are concentrated intracellularly, which c Those teaching about the subject at both undergraduate and is the usual site of replication of these pathogens. As such, we postgraduate level. conclude that the term ‘‘atypical pathogens’’ is still useful to The guidelines have been developed to apply to the UK clinicians in guiding discussion about aetiology and manage- healthcare system and population, but they might also be of ment of CAP. value to other countries which operate similar healthcare iii8 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

services, with appropriate modification to take into account c The processes for managing acutely ill medical patients Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from differences in licensing and availability of antimicrobial agents. admitted to hospital have undergone important changes. The specialty of acute medicine has developed substantially and, in many hospitals, teams run by acute medicine 1.5 What patient populations are we including and excluding? physicians are already taking responsibility for the early These guidelines address the management of unselected adults stages of acutely ill medical patients. This shift, together with CAP who are managed by their general practitioner or with the demands on junior doctors’ hours arising from the admitted to hospital as an emergency. European Working Time Directive, mean that patient care Although there are similarities in the principles of manage- increasingly involves different teams of doctors. Effective ment between pneumonic lower respiratory tract infection (ie, handover between teams, careful patient review and CAP) and non-pneumonic lower respiratory tract infection, coherent clinical guidelines are key aspects of patient there are differences in the aetiology, severity assessment, management in this context.14 management and outcome. Recommendations for the antibiotic c Timeliness of treatment has enlarged as a priority in clinical management of acute exacerbations of chronic obstructive care processes. This is perhaps most evident in the ‘‘4-hour pulmonary disease (COPD) are included in the guideline on the admission to treatment’’ target applied to emergency management of COPD published by the National Institute of departments across the UK.15 Increased attention to speed Health and Clinical Excellence (NICE).7 to treatment as a measure of performance may have the We do not consider the management of pneumonia in: inadvertent effect of increasing the inappropriate or c Patients where the pneumonia is an expected terminal event excessive use of antibiotics in patients with suspected but or who are known to have lung cancer, pulmonary unconfirmed CAP, thus exacerbating any existing problems tuberculosis or cystic fibrosis or primary immune deficiency with HCAIs (see Section 8.9). or secondary immune deficiency related to HIV infection, or c Newer microbiological tests for the detection of infection by drug or systemic disease-induced immunosuppression. We respiratory pathogens such as urine antigen tests are do include patients receiving oral corticosteroid therapy as becoming increasing available routinely, while previously this is a not uncommon situation for patients admitted on established tests such as complement fixation tests are medical take. gradually being phased out. c Patients who have been in hospital within the previous 10 days and may have hospital acquired pneumonia. 1.7 Guidelines Committee membership Patients admitted from healthcare facilities such as nursing The Guidelines Committee was established in January 2008 homes and residential homes will be commented on with representatives from a range of professional groups separately. including the Royal College of General Practitioners, Royal c Children with CAP (please refer to the BTS guidelines for College of Physicians, British Geriatric Society, British Infection 8 the management of CAP in childhood ). Society, British Society for Antimicrobial Chemotherapy, General Practice Airways Group, Health Protection Agency 1.6 What changes have happened in the area of CAP since the and the Society for Acute Medicine (see Section 11). Three http://thorax.bmj.com/ 2004 guidelines? members in the current committee also served on the 2001 and 2004 Guidelines Committee. c Concerns regarding health care-associated infections (HCAIs), particularly methicillin-resistant Staphylococcus The Guidelines Committee agreed the remit of the guidelines. aureus (MRSA) and Clostridium difficile infection, have The Centre for Reviews and Dissemination and Centre for grown in recent years. These HCAIs are associated with Health Economics at the University of York was commissioned volume of antibiotic use. Antibiotic stewardship should by the BTS to undertake literature searches on behalf of the now be an essential responsibility for all clinicians. Measures Guidelines Committee. to avoid and reduce inappropriate antibiotic use are there- on October 1, 2021 by guest. Protected copyright. fore at the forefront of management strategies for all 1.8 How the evidence was assimilated into the guidelines 9 infective episodes. 1.8.1 Literature searches c Fluoroquinolone antibiotics with enhanced activity against Systematic electronic database searches were conducted in order Gram-positive organisms (the so-called ‘‘respiratory quino- to identify potentially relevant studies for inclusion in the CAP lones’’ such as levofloxacin and moxifloxacin) have been guidelines. For each topic area the following databases were widely available for some years now. Their activity against searched: Ovid MEDLINE (including MEDLINE In Process), most major respiratory pathogens led initially to widespread Ovid EMBASE, Ovid CINAHL and the Cochrane Library use of these antibiotics for respiratory tract infections, (including the Cochrane Database of Systematic Reviews, the including CAP. However, more recently these antibiotics Database of Abstracts of Reviews of Effects, the Cochrane have been associated with both methicillin-resistant S aureus (MRSA) and C difficile infections.10 11 This has promoted Central Register of Controlled Trials, the Health Technology increasing pressure to limit the use of these antibiotics in Assessment database and the NHS Economic Evaluation favour of other classes of antibiotics where appropriate.9 Database). The searches were first run in December 2007 and were c Antimicrobial resistance in Streptococcus pneumoniae was updated in August 2008. Searches included a combination of noted to rise in the late 1990s. Fortunately, a reversal of this trend has been observed in the last 5 years, with rates of indexing terms and free text terms, and were limited to English penicillin-resistant S pneumoniae in the UK remaining below language publications only. Full search strategies for each 4% (see Section 8.4). database are available in the web-based supplement. c Pneumonia admissions to hospital rose by 34% between 1997–8 and 2004–5.12 This was matched by an increase in 1.8.2 Appraisal of the literature admissions to intensive care units for CAP13 (see Section One individual (HR) read the title and abstract of each article 2.1). retrieved by the literature searches and decided whether the

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii9 BTS guidelines paper was definitely relevant, possibly relevant or not relevant Table 1 Brief description of the generic levels of evidence and Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from to the project. For each unique paper in the first and second guideline statement grades used category, the full paper was ordered and allocated to the Evidence Guideline relevant section(s). level Definition statement grade The initial searches (2003–7) identified 7449 reference Ia A good recent systematic review of studies A+ abstracts, of which 1603 were definitely or possibly relevant designed to answer the question of interest after the first screen. These were divided into groups as follows: Ib One or more rigorous studies designed to answer A2 aspiration/institutional pneumonia (141); C difficile infection the question, but not formally combined related (66); pneumonia on critical care (161); aetiology (154); II One or more prospective clinical studies which B+ antibiotic therapy (420); clinical features (46); community illuminate, but do not rigorously answer, the question investigations and management (68); complications and failure III One or more retrospective clinical studies which B2 to improve (37); general investigations and management (288); illuminate, but do not rigorously answer, the incidence and epidemiology (55); microbiology investigations question (86); prevention (232); radiology (15); severity assessment (134). IVa Formal combination of expert views C The second search (2007–8) identified 1143 reference IVb Other information D abstracts, of which only 177 were definitely or possibly relevant. A fuller description is given in Section 1 and Appendices 1–4. These were divided into the same groups: aspiration/institu- tional pneumonia (11); C difficile infection related (5); pneumo- comment on any newly licensed and relevant antibiotics and nia on critical care (10); aetiology (22); antibiotic therapy (36); issue guideline updates or revisions as necessary. Important clinical features (0); community investigations and manage- changes will be posted on the BTS website (www.brit-thoracic. 16 ment (3); complications and failure to improve; general org.uk). The membership of the Guideline Committee will investigations and management (20); incidence and epidemiol- change over time on a rolling programme dictated by the BTS ogy (8); microbiology investigations (10); prevention (9); Standards of Care Committee policy for the Guideline radiology (2); severity assessment (26). Committee membership. A total of 547 papers were retrieved and circulated for critical appraisal. The leads for each section independently judged the 1.11 Implementation of the guidelines clinical relevance and scientific rigour of each paper assigned to them using generic study appraisal checklists (see Appendices 1 We expect that these guidelines will act as a framework for local and 2) adapted from published checklists.17–20 The reliability of development or modification of protocols after discussion with the evidence in each study was graded from Ia to IVb using a local clinicians and management. The subsequent dissemina- generic list of evidence levels (see Appendix 3) developed from tion, implementation and evaluation of these guidelines should existing insights and checklists.21 22 Disagreements were resolved be undertaken by the hospital Quality and Clinical Effectiveness by discussion with the section partner (see Section 11.2). Where Group in conjunction with relevant committees such as those relevant, individual references used in this document are responsible for therapeutics, antibiotic prescribing or protocol development. Countries with similar health service systems will followed by an indication of the evidence level in square http://thorax.bmj.com/ brackets. also find the framework of value, adapting the guidelines to take Section leads individually assessed the literature selected and into account any relevant national differences in disease wrote a short document describing study findings and related presentation and the availability of investigations and anti- recommendations. These documents were discussed by the microbial agents. whole committee. 1.12 Auditing CAP management 1.8.3 Drafting of the guidelines The management of CAP is a sufficiently common and

important issue to warrant the development of audit measures on October 1, 2021 by guest. Protected copyright. The Guidelines Committee corresponded by email on a regular of the process of care and outcome to evaluate the quality of basis throughout the duration of the guideline development. care for CAP, using guidelines as a standard of management. Meetings of the full group were held in February 2008, July 2008 An audit tool has been developed and is available through the and November 2008. Each section lead edited the corresponding BTS website (www.brit-thoracic.org.uk). section in the 2001 guidelines document, incorporating all relevant literature and recommendations from the 2004 update and the current update. In December 2008 the guidelines were SECTION 2 INCIDENCE, MORTALITY AND ECONOMIC discussed at an open plenary session at the BTS Winter CONSEQUENCES Conference. A revised draft guidelines document was circulated 2.1 How common is adult CAP in the community and in hospital? to professional bodies for endorsement in January 2009 and to Prospective population studies from the UK,23 [II] Finland24 [Ib] the BTS Standards of Care Committee in March 2009. and North America25 [Ib] have reported an annual incidence of CAP diagnosed in the community of between 5 and 11 per thousand adult population. Pneumonia, diagnosed clinically by 1.9 Grading of recommendations general practitioners, accounts for only 5%23 [Ib] to 12%26 [Ib] of all Recommendations were graded from A+ to D (table 1) as cases of adult lower respiratory tract infection treated with indicated by the strength of the evidence as listed in the table in antibiotics by general practitioners in the community in the UK. Appendix 4. The incidence varies markedly with age, being much higher in the very young and the elderly. In a Finnish study the annual 1.10 Plans for updating these guidelines incidence in the 16–59 age group was 6 per 1000 population, for Following the BTS protocol for guidelines revisions, the those aged >60 years and 34 per 1000 population for those aged Committee will meet on an annual basis and review new >75 years.24 [Ib] A similar pattern was reported from Seattle, published evidence obtained from a structured literature search, USA.25 [Ib] iii10 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

Population-based studies of the incidence of CAP requiring 2.2 What is the mortality of CAP? Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from hospitalisation have reported overall incidences of 1.1 per 1000 The reported mortality of adults with CAP managed in the adult population per annum in Canada,27 [Ib] 2.6 per 1000 in community is low and less than 1%.15 23 32 [II] [Ib] [Ib] Deaths in the Spain,6 [II] 2.7 per 1000 population in Ohio, USA6 [Ib] and 4 per community due to CAP are rare in the UK. In one study only 1000 population in Pennsylvanian hospitals, USA.28 [III] seven cases were identified by coroners’ post mortems over Increasing age was associated with an increasing incidence of 1 year in Nottingham, a large urban city of three quarters of a admission to hospital with CAP in Canada; from 1.29 per 1000 million, giving an incidence of 1 per 100 000.23 [III] persons aged 18–39 years, to 1.91 per 1000 persons aged 40– The reported mortality of adults hospitalised with CAP has 54 years, to 13.21 per 1000 persons aged 55 years or above.29 [III] varied widely. The BTS multicentre study reported a mortality A study of Hospital Episode Statistics for England between 1997 of 5.7%,6 [II] but did not study patients over the age of 74 years. and 2005 showed a rise in hospital admissions for pneumonia Other UK studies have reported mortalities of 8%,35 [II] 12%36 [Ib] over time. The age-standardised incidence of hospitalisations and 14%.37 [Ib] Countries with similar healthcare systems have with a primary diagnosis of pneumonia increased by 34% reported hospital mortality rates of 4%,24 [Ib] 7%,38 [II] 8%241 [Ib] between 1997–8 and 2004–5, from 1.48 to 1.98 per 1000 and 10%.39 [Ib] population. This increase was more marked in older adults.12 [III] The longer term mortality of CAP is high, reflecting the The proportion of adults with CAP who require hospital frailty of many patients who develop CAP in the first instance. admission in the UK has been reported as between 22%23 [Ib] and In a US study the 90-day all-cause mortality was 8.7% and 42%.30 [III] This figure varies in other countries, probably mortality at 5.9 years was 39.1%. Age, level of education, male dependent on the structure of the primary and secondary sex and nursing home residence were independently associated healthcare system. In a Finnish prospective longitudinal with long-term mortality.40 [II] Other studies found long-term population study, 42% were admitted to hospital.24 [Ib] A 50% mortality to be 20.8% at 1 year, 34.1% at a mean of 901 days admission rate was reported in one study from Spain, but this and 35.8% at 5 years.41 [II] only included patients referred by their general practitioner to The mortality of patients with severe CAP requiring the hospital emergency service for confirmation of the diagnosis admission to an ICU is high. This is likely to be particularly of CAP.10 [II] evident in health services such as the National Health Service In Seattle, USA 15% were hospitalised.31 [Ib] In the Pneumonia where ICU beds are at a premium, such that only critically ill Patient Outcomes Research multicentre prospective cohort patients in need of assisted ventilation can be admitted. ICU- study of CAP in America, 41% of adults studied were managed based studies in the UK have reported mortalities of over initially as outpatients and the remainder were admitted to 50%,25 34 42 43 [III] [III] [III] [III] although a more recent analysis of hospital. Of those initially treated as outpatients, only 7.5% admissions to ICUs across England, Wales and Northern Ireland were subsequently admitted, 56% because of the CAP and the between 1995 and 2004 reported a mortality of 34.9% for rest because of worsening of a comorbid illness.32 [Ib] patients with CAP.13 [III] Nearly all of the patients required The proportion of adults hospitalised with CAP who require assisted ventilation. By contrast, the mortality rate in a large management on an intensive care unit (ICU) varies from 1.2% multicentre study of severe CAP in four French ICUs reported a 12 [II] 65 25 [Ib] in one Spanish study and 5% in the BTS multicentre study mortality of 35% with a ventilation rate of only 52%. http://thorax.bmj.com/ [II] to 10% in another Spanish study.33 [II] Previously, between Similar figures were reported from another ICU-based study in 8%13 [II] and 10%34 [III] of medical admissions to an ICU were France.44 [II] In a specialist ICU in Spain, a mortality of 22% was found to be for severe CAP. An analysis of admissions to ICUs reported, rising to 36% in the 61% of patients who required across England, Wales and Northern Ireland between 1995 and assisted ventilation.33 [II] 2004 found CAP to be the cause of 5.9% of all ICU admissions. There was an increase in CAP requiring intensive care from 12.8 Summary per unit in 1996 to 29.2 per unit in 2004. This represented an c The reported mortality of adults with CAP managed in the increase of 128% compared with a rise in the total number of on October 1, 2021 by guest. Protected copyright. community in the UK is very low and less than 1%. [Ib] admissions to ICUs of only 24%.13 [III] c The reported mortality of adults hospitalised with CAP in the UK has varied between 5.7% and 14%. [Ib] Summary c The mortality of patients with severe CAP requiring c The annual incidence in the community is 5–11 per 1000 admission to an ICU in the UK is high at over 30%. [III] adult population. [Ib] c The long-term mortality of CAP is between 35.8% and c CAP accounts for 5–12% of all cases of adult lower 39.1% at 5 years. [II] respiratory tract infection managed by general practitioners in the community. [Ib] 2.3 What are the economic consequences of CAP? c The incidence varies markedly with age, being much higher A prevalence-based burden of illness study estimated that CAP in the very young and the elderly. [Ib] in the UK incurred a direct healthcare cost of £441 million c Between 22% and 42% of adults with CAP are admitted to annually at 1992–3 prices. The average cost for managing hospital. [Ib] pneumonia in the community was estimated at £100 per c The incidence for patients requiring admission to hospital episode compared with £1700–5100 when the patient required varies with age from 1.29 per 1000 persons aged 18–39 years admission to hospital. Hospitalisation accounted for 87% of the up to 13.21 per 1000 persons aged >55 years. [III] total annual cost.30 [III] c The age-standardised incidence of admission to hospital A similar exercise conducted in 1997 in the USA calculated increased by 34% from 1.48 to 1.98 per 1000 population that annual costs of CAP amounted to $8.4 billion, 52% of the between 1997–8 and 2004–5 in England. costs being for the inpatient care for 1.1 million patients and the c Between 1.2% and 10% of adults admitted to hospital with remaining costs for the 4.4 million outpatient consultations. CAP are managed on an ICU. [II] The average hospital length of stay varied between 5.8 days for

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii11 BTS guidelines

those under 65 years of age and 7.8 days for older patients.45 [III] references), grouped together by where patients have been Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from A prospective study of costs and outcome of CAP from five managed—be it in the community, in hospital or on an ICU. For hospitals in North America concluded that costs of antibiotic all these groups, a common range of pathogens is regularly therapy varied widely but had no effect on outcome or identified as causes of CAP. [Ib] Although a single pathogen is mortality. Patients treated in the hospitals with the lowest identified in 85% of patients where an aetiology is found, the costs did not have worse medical outcomes.46 [Ib] true frequency of polymicrobial CAP is not known and observed figures are dependent on the intensity of investigation. S Summary pneumoniae is the most frequently identified pathogen. [Ib] The relative frequency of pathogens in patients managed in the c The direct costs associated with CAP are high and mostly community and in hospital is probably similar, but the absence associated with inpatient care costs. [III] of more than one study in the community makes further c Substantial costs savings could likely be made by strategies conclusions uncertain. Legionella species and S aureus are to prevent CAP, to reduce the requirement for hospital identified more frequently in patients managed on the ICU. admission and to shorten the length of hospital stay. [III] [Ib] The apparent difference in the frequency of Mycoplasma pneumoniae may depend on whether or not a study is performed 2.4 What comments can be made about cost effectiveness of in an epidemic year. [II] Gram-negative enteric bacilli, different therapies? Chlamydophila psittaci and Coxiella burnetii are uncommon We are not able to provide any structured guidance on this causes of CAP. [Ib] subject. Modern guidelines should attempt to provide informa- Since 2001 only one additional study of adults admitted to tion, not only on clinical management but also on the assessment hospital with CAP has been published,47 which found a similar of robust published data on cost effectiveness of therapies. distribution of common causative pathogens to that in previous However, it was noted that there is a clear deficiency of good studies. quality comparative clinical data which would allow meaningful comparisons of management and antibiotic strategies for CAP, whether assessing for clinical or cost effectiveness outcome. 3.3 What are the causes of adult CAP in similar populations elsewhere in the world? The results and references of relevant studies from the Summary remainder of Europe, Australia and New Zealand and North c We have not attempted a systematic appraisal of current America were compared in the earlier BTS guidelines.1 Other pharmacoeconomic evidence for CAP and do not give a European studies confirm previous knowledge.30 31 48 [Ib] [Ib] [II] For structured view on cost effectiveness. patients managed in the community and in hospital, the c Cost effectiveness data pertinent to UK practice does not frequency of pathogens is broadly similar to that in the UK. [II] exist at the time of writing and is an area for further This suggests that aspects of these guidelines will be applicable research. to other countries as well as the UK. The absence of studies using sensitive methods for pneumococcal polysaccharide http://thorax.bmj.com/ SECTION 3 AETIOLOGY AND EPIDEMIOLOGY capsular antigen detection for the identification of S pneumoniae 3.1 Introduction may be the explanation for the lower frequency outside the UK. No two studies of the aetiology of CAP are the same. Apparent The apparent differences in M pneumoniae may relate to the differences in the observed frequency of pathogens, while presence or absence of epidemics at the time of the study. possibly real, may also be due to a number of other factors Chlamydophila pneumoniae is identified frequently in some 31 [Ib] including healthcare delivery (distribution of management European countries, but recent studies in Germany and 31 [II] between primary and secondary care, hospital and ICU the Netherlands found frequencies of only 0.9% and 3%, respectively. admission practices), population factors (such as age mix, the on October 1, 2021 by guest. Protected copyright. frequency of alcoholism, comorbid diseases, immune suppres- Antibiotic-resistant S pneumoniae appears to be no more sion and malignancy) and study factors (type and number of frequent in severely ill patients admitted to the ICU than in samples collected, investigations performed, result interpreta- those managed on an ordinary hospital ward in a country where 49 [Ib] tion). Frequently, such details are not explicitly stated in the such resistance is common. Studies of patients with severe study methodology and, although we have not included studies CAP from Europe suggest a lower frequency of legionella and a which do not comply with certain standards, apparently similar higher frequency of Gram-negative enteric bacilli infections studies may hide very different methodology. With the compared with the UK. These may be real or methodological. exception of elderly subjects, few adequately powered studies [IVa] using the same methodology have been used to compare A frequency of 8% for non-pneumophila legionella species different population groups. Conclusions about observed was found in one Dutch study.32 [II] A study of hospitalised differences in the following data must therefore be treated patients in Spain50 [Ib] found a frequency of mixed aetiology of with caution. 13%, similar to the average figure of 11% for the UK. Another Many of the statements in the following text arise from a Spanish study found a frequency of 5.7%.51 [Ib] A recent comparison of studies, rather than data from individual studies publication showed a high frequency of C burnetii infection in that have set out to answer that question. For this reason, the Canary Islands.52 [Ib] evidence grades follow statements to justify that conclusion, as well as individual references. 3.4 How does the aetiology differ in certain geographical areas? Specific studies suggest a higher frequency of certain pathogens 3.2 What are the causes of adult CAP in the UK? in some geographical areas as described in the 2001 BTS These are set out in table 2, together with details of the relevant guidelines (table 3).1 A global study found a frequency of references (and grading of evidence from those individual atypical pathogens of 20–28% of cases in different regions of the iii12 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

Table 2 Studies of community acquired pneumonia (CAP) conducted in the UK Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from Where managed Community Hospital Intensive care unit 1 study* (n = 236) 5 studies{ (n = 1137) 4 studies{ (n = 185)

Streptococcus pneumoniae 36.0 (29.9 to 42.1) 39 (36.1 to 41.8) 21.6 (15.9 to 28.3) Haemophilus influenzae 10.2 (6.3 to 14.0) 5.2 (4.0 to 6.6) 3.8 (1.5 to 7.6) Legionella spp 0.4 (0.01 to 2.3) 3.6 (2.6 to 4.9) 17.8 (12.6 to 24.1) Staphylococcus aureus 0.8 (0.1 to 3.0) 1.9 (1.2 to 2.9) 8.7 (5.0 to 13.7) Moraxella catarrhalis ? 1.9 (0.6 to 4.3) ? Gram-negative enteric bacilli 1.3 (0.3 to 3.7) 1.0 (0.5 to 1.7) 1.6 (0.3 to 4.7) Mycoplasma pneumoniae 1.3 (0.3 to 3.7) 10.8 (9.0 to 12.6) 2.7 (0.9 to 6.2) Chlamydophila pneumoniae ? (?) 13.1 (9.1 to 17.2) ? (?) Chlamydophila psittaci 1.3 (0.3 to 3.7) 2.6 (1.7 to 3.6) 2.2 (0.6 to 5.4) Coxiella burnetii 0 (0 to 1.6) 1.2 (0.7 to 2.1) 0 (0 to 2.0) All viruses 13.1 (8.8 to 17.4) 12.8 (10.8 to 14.7) 9.7 (5.9 to 14.9) Influenza A and B 8.1 (4.9 to 12.3) 10.7 (8.9 to 12.5) 5.4 (2.6 to 9.7) Mixed 11.0 (7.0 to 15.0) 14.2 (12.2 to 16.3) 6.0 (3.0 to 10.4) Other 1.7 (0.5 to 4.3) 2 (1.3 to 3) 4.9 (2.3 to 9.0) None 45.3 (39.0 to 51.7) 30.8 (28.1 to 33.5) 32.4 (25.7 to 39.7) Values are mean (95% CI) percentages. *Reference 39[Ib]. {References 10[Ib],11[Ib],13[Ib],14[Ib],68[Ib]. {References 20[Ib],21[Ib],65[Ib],72[II]. world.53 [II] A similar figure of 23.5% was found in a multicentre 3.5 Is the aetiology different in specific population groups? South Asian study.54 [Ib] Elderly subjects Studies from Chile55 [Ib] and Nicaragua56 [Ib] report a similar Three UK studies (two using a definition of ‘‘elderly’’ of pathogen spectrum to previous European studies. .65 years of age but excluding those aged .79 years (quoted Evidence of legionella infection was found in 31.7% of non- in Venkatesan et al69 [Ib]) and one study using a definition of consecutive pneumonia cases in Trinidad57 [II] and 5.1% of 645 .75 years37 [Ib]) have reported data on the comparative consecutive cases in Brazil.58 [Ib] An incidence of 5.2% for C frequency of pathogens in elderly subjects compared with that pneumoniae was found by the same group,58 [II] with a frequency in a younger population. The results are combined in fig 3. For of 8.1% being found in a Canadian study.59 [II] In 62% of these most pathogens their frequency is the same in young as in old cases an additional pathogen was also found. subjects, but M pneumoniae and legionella infection are less http://thorax.bmj.com/ An outpatient study in Arizona found evidence of coccidioi- frequent in elderly people. [Ib] M pneumoniae and other atypical domycosis in 29% (16–44%) of 55 cases.60 [II] pathogens were found to occur more frequently in patients aged Studies from south and east Asia found high frequencies of S ,60 years in one other study.70 [Ib] H influenzae may also be more pneumonia,61 62 [Ib] C pneumonia61 [Ib] and Gram-negative bac- commonly identified in elderly patients [II]. Gram-negative teria61 62 [Ib] and Haemophilus influenzae63 [Ib] in Thailand. In enteric bacilli were no more common in elderly patients [III], China, H influenzae was the predominant pathogen in one although this has been reported in at least one other study.71 [II] study,64 [Ib] but S pneumoniae and M pneumoniae in another.65 [Ib] S No difference in the frequency of pathogens according to age 66 [II] 72 [III]

pneumoniae followed by H influenzae predominated in Japan, was found in one study of patients with severe CAP. on October 1, 2021 by guest. Protected copyright. and S pneumoniae followed by M pneumoniae in Taiwan.67 [Ib] One study from Spain compared the aetiology in those aged S pneumoniae and Klebsiella pneumoniae were found to be the .79 years and ,80 years and confirmed the previous findings most frequent causes of CAP in the ICU on an Indian Ocean of less M pneumoniae and legionella infection and more island.68 [Ib] aspiration and unknown aetiology in the elderly patients, but did not confirm a greater frequency of S pneumoniae in elderly subjects (fig 4).73 [Ib]

Table 3 Pathogens which are more common as a cause of community Patients with chronic obstructive pulmonary disease (COPD) acquired pneumonia in certain geographical regions There are no relevant UK studies and no new data. H influenzae Pathogen Geographical area References and M catarrhalis may be more frequent. One Danish study directly compared those with and without COPD and found no Legionella spp Countries bordering the 27[II], 378[II] Mediterranean Sea difference in pathogen frequency; however, numbers were small 74 [II] Coxiella burnetii North-west Spain 389[II] so real differences may have been missed. A Spanish study Coxiella burnetii Canada 390[II] which focused on patients with COPD but with no control Klebsiella pneumoniae South Africa 391[II], 392[II] group found a pathogen distribution similar to that described in 75 [II] Burkholderia pseudomallei South-east Asia and 93[II], 393[II], 394[II], 395[II] studies of CAP in the general population. A further Spanish northern Australia study found S pneumoniae, Enterobacteriaceae, Pseudomonas Gram-negative enteric Italy 379[II] aeruginosa and mixed infections to occur more frequently in bacilli those with chronic lung disease.75 [Ib] In one study COPD was Mycobacterium Non-industrialised countries 93[II],94[II] tuberculosis found more frequently in patients with bacteraemic pneumo- coccal pneumonia than other CAPs.76 [Ib]

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii13 BTS guidelines

Figure 3 Difference in causative Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from pathogens between young and elderly patients. Vertical axis shows the difference in frequency between the young and the elderly groups for pooled data from three UK studies (percentages ¡95% confidence intervals). Sp, Streptococcus pneumoniae; Hi, Haemophilus influenzae; Lp, Legionella spp; Sa, Staphylococcus aureus; Mcat, Moraxella catarrhalis; GNEB, Gram-negative enteric bacilli; Mp, Mycoplasma pneumoniae; Cp, Chlamydophila pneumoniae; Cpsi, Chlamydophila psittaci; Cb, Coxiella burnetii; allV, viruses; Flu, influenza viruses; oth, other organisms; none, no pathogen identified. Taken from Venkatesan et al69 and Lim et al.37

Patients with diabetes (HCAP) which included 25.4% from a nursing home found a Diabetes was found to be more frequent in patients with higher frequency of aspiration pneumonia, H influenzae, Gram- bacteraemic pneumococcal pneumonia than in those with either negative bacilli and S aureus and a lower frequency of legionella non-bacteraemic pneumococcal pneumonia or all CAPs in one and ‘‘no pathogen’’ in the HCAP group compared with the non- study.76 [Ib] No new data were found. HCAP group.81 [Ib]

Nursing home residents Alcoholic patients Aspiration,76 77 [II] [II] Gram-negative enteric bacilli78 [III] and There are no UK studies. Aspiration,72 [II] pneumococcal anaerobes [IVb] may be more frequent than in matched elderly infection overall,49 [Ib] bacteraemic pneumococcal infection,49 76 [Ib] [II] 71 [II] 82 [III] patients. North American studies, which suggest these differ- Gram-negative enteric bacilli, legionella, atypical 49 [Ib] 49 [Ib] ences, may not be relevant to the UK population and healthcare pathogens, C pneumoniae, anaerobes [IVb] and mixed 49 [Ib] system. Legionella infections and atypical pathogens are infections may be more frequent. A further study of uncommon.579 [II] [III] The first UK prospective cohort study hospitalised patients in Spain found an association with current or ex alcoholism and S pneumoniae infection.83 [Ib]

comparing 40 patients with nursing home acquired pneumonia http://thorax.bmj.com/ with 236 adults aged >65 years with CAP80 [Ib] found no evidence that the distribution of causative pathogens is different Patients on oral steroids from that in other older adults with CAP. A comparative study There are no UK studies and no new data. Infection with from Spain of patients with health care associated pneumonia Legionella species may be more frequent.84 [III]

Figure 4 Comparative frequency of identification of pathogens in elderly and on October 1, 2021 by guest. Protected copyright. young patients in European studies that have contemporaneously applied the same methodology to both groups. Results of four studies totalling 2193 patients (566 elderly patients defined as .60, .65 and .79 years).69 70 73 502 [II] [II] [II] [II] For each organism, the frequency (¡95% confidence intervals) in elderly patients is shown in the left bar and in young patients in the right bar. Sp, Streptococcus pneumoniae; Hi, Haemophilus influenzae; Lp, Legionella spp; Sa, Staphylococcus aureus; Mcat, Moraxella catarrhalis; GNEB, Gram-negative enteric bacilli; Mp, Mycoplasma pneumoniae; Cp, Chlamydophila pneumoniae; Cpsi, Chlamydophila psittaci; Cb, Coxiella burnetii; allV, viruses; Flu, influenza viruses; oth, other organisms; none, no pathogen identified.

iii14 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

Aspiration pneumonia Staphylococcus aureus Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from There are no UK studies. Most studies of CAP exclude such It is more common in the winter months. Coincident influenza- patients. Anaerobic bacteria and Gram-negative enteric bacilli type symptoms are reported in 39% (95% CI 27% to 53%) of may be more common (see the section above on elderly cases.63536102[II] Evidence of coincident influenza virus infection subjects).72 85 [III] [III] is found in 39% (95% CI 17% to 64%) of those admitted to hospital,63536102 [II] and 50% (95% CI 25% to 75%) of those admitted to an ICU.33 34 42 103 [II] Congestive cardiac failure Multiple case reports104–118 [III] and series of 2–11 patients,119–124 A study from Spain suggested a higher frequency of this [II] both from the UK and worldwide, describe episodes of CAP condition (31%) in those with viral pneumonia than in those caused by S aureus (either methicillin-sensitive S aureus (MSSA) with mixed (8%) or pneumococcal pneumonia (2%).86 [Ib] or MRSA) capable of production of the Panton-Valentine Leucocidin toxin. Severe illness—with high mortality, bilateral 3.6 What are the epidemiological patterns of pathogens causing lung shadowing and frequent lung cavitation—is common to CAP and is this information useful to the clinician? these reports. No prospective studies have been performed to identify the true frequency of CAP due to this organism, but it Streptococcus pneumoniae appears to be rare at present. S pneumoniae occurs most commonly in the winter [II].87 [II] Outside the UK, epidemics have occurred in overcrowded Influenza virus settings (eg, mens’ shelters and prisons) [II].87 88 [II] [II] Annual epidemics of varying size are seen during the winter months.125 [II] Pneumonia complicates 2.9% (95% CI 1.4% to Legionella species 5.4%) of cases in the community.126 [Ib] The frequency of Legionella infection was most common between June and staphylococcal pneumonia in patients with influenza symp- October, with a peak in August and September in the UK toms is not known. Of adults with CAP admitted to UK between 1999 and 2005.89 [II] Fifty percent of UK cases are hospitals in whom influenza infection is confirmed, 10% (95% related to travel,89 93% of these relating to travel abroad.89 [II] CI 4.1% to 19.5%) have coincident S aureus infection. [II] Of Clusters of cases are linked to Mediterranean resorts, especially those admitted to an ICU, the corresponding figure is 67% (95% 34 42 43 103 [II] France, Greece, Turkey and Spain,89 [II] but only 23%90 91 [II] of CI 35% to 90%). cases occur in clusters. Epidemics occur related to water- containing systems in buildings.92 [II] Summary c The low frequency of legionella, staphylococcal, C psittaci and C burnetii infection in patients with CAP in both the Mycoplasma pneumoniae community and in hospital, together with the likely high Epidemics spanning three winters occur every 4 years in the UK, frequency of the relevant risk factors (outlined above) in the as shown in fig 5. The apparent decline in reports is probably general population suggests that routine enquiry about such related to decreased use of complement fixation testing rather factors is likely to be misleading. [IV] http://thorax.bmj.com/ than a true decline in frequency. c Only in those with severe illness where the frequency of legionella and staphylococcal infection is higher may enquiry about foreign travel and influenza symptoms be Chlamydophila pneumoniae of predictive value. [IV] Epidemics occur in the community and in closed commu- c Knowledge of increased mycoplasma activity in the com- 93–95 [II] [II] [II] nities. Its direct pathogenic role as a cause, as munity during an epidemic period may help guide the opposed to being associated with CAP, is not clear. The lack of a clinician to the increased likelihood of mycoplasma infec- diagnostic gold standard means the frequency is unknown. tion. [IV] on October 1, 2021 by guest. Protected copyright. Serological and PCR96 [Ib] results are highly variable between assays. Evidence that antibiotic therapy directed against this SECTION 4 CLINICAL FEATURES organism alters the course of the illness is lacking. When 4.1 Can the aetiology of CAP be predicted from clinical features? identified, other bacterial pathogens (eg, S pneumoniae) are often There have been a large number of publications looking at the identified in the same host.97–99 [II] [II] [II] Patients may recover possibility of predicting the aetiological agent from the clinical when antibiotics to which C pneumoniae is not sensitive are features at presentation; however, while certain symptoms and given.99 [II] signs are more common with specific pathogens, none allow accurate differentiation.127 128 [II] This led to a suggestion that the Chlamydophila psittaci term ‘‘atypical’’ pneumonia be abandoned.128 As explained in Infection is acquired from birds and animals but human to Section 1.3.2, the term ‘‘atypical pathogens’’ remains useful and human spread may occur. [II] Epidemics are reported in relation there is evidence that pleuritic pain is less likely in pneumonia to infected sources at work (eg, poultry or duck workers). [II] secondary to these agents.129 Only 20% of UK cases have a history of bird contact.100 [II] Summary Coxiella burnetii c The likely aetiological agent causing CAP cannot be Cases are most common in April to June, possibly related to the accurately predicted from clinical features. [II] lambing and calving season. [II] Epidemics occur in relation to c The term ‘‘atypical’’ pneumonia should be abandoned as it animal sources (usually sheep), but a history of occupational incorrectly implies that there is a characteristic clinical exposure is only present in 7.7% (95% CI 6.2% to 9.4%) of presentation for patients with infection caused by ‘‘atypi- cases.101 [II] cal’’ pathogens. [II]

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii15 BTS guidelines

Figure 5 Laboratory reports to the Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from Health Protection Agency Centre for Infections of infections due to Mycoplasma pneumoniae in England and Wales by date of report, 1990–2008 (4-weekly).

4.2 Specific clinical features of particular respiratory pathogens agree that it remains impossible to accurately differentiate on Clinical features associated with specific pathogens are clinical grounds.131 132 Studies have reported L pneumophila to be described below and summarised in box 1. more common in men,133 in young patients with lower rates of comorbid illness,134 in smokers135 and in those who have already 133 135 Streptococcus pneumoniae received antibiotic therapy. Clinical features which might One study using discriminant function analysis found pneu- point towards L pneumophila as an aetiological agent include mococcal aetiology to be more likely in the presence of encephalopathy and other neurological symptoms, gastrointest- cardiovascular comorbidity, an acute onset, pleuritic chest pain inal symptoms, more severe infection, elevated liver enzymes, and less likely if patients had a cough or flu-like symptoms or elevated creatine kinase and relatively less frequent upper had received an antibiotic before admission.130 [III] respiratory tract symptoms, pleuritic chest pain and purulent 82 133 136 Bacteraemic pneumococcal pneumonia was found to be more sputum. likely in those patients who had at least one of the following features: female, history of no cough or a non-productive cough, Mycoplasma pneumoniae 76 [II] history of excess alcohol, diabetes mellitus or COPD. One study has compared CAP due to M pneumoniae to patients http://thorax.bmj.com/ In high severity CAP where patients were admitted to an with pneumococcal or legionella pneumonia. It reported that ICU, clinical features had little value in predicting the patients with mycoplasma pneumonia were younger, less likely aetiological agent with the exception of those patients with to have multisystem involvement and more likely to have fever (.39uC) or chest pain who were statistically more likely to received an antibiotic before admission.23 By contrast, another 44 [II] have pneumococcal pneumonia. report found no distinctive clinical features in patients with confirmed M pneumoniae pneumonia.137 [II] Legionella pneumophila A variety of clinical features have been found to be more Chlamydophila pneumoniae on October 1, 2021 by guest. Protected copyright. common in patients with legionella pneumonia, and yet most A comparative study of patients with C pneumoniae and S pneumoniae pneumonia found the former more likely to present with headaches and a longer duration of symptoms before 95 Box 1 Some clinical features reported to be more common hospital admission. [II] A study from Israel reported no with specific pathogens (references are given in the text) distinguishing clinical features for chlamydial pneumonia, except that it affected older patients than pneumococcal and mycoplasma infections.98 [II] A comparison of C pneumoniae and c Streptococcus pneumoniae: increasing age, comorbidity, M pneumoniae confirmed the age difference between the groups acute onset, high fever and pleuritic chest pain. and stated that, although clinical features could not be used to c Bacteraemic S pneumoniae: female sex, excess alcohol, diabetes distinguish between the two, cough, hoarseness and rhinitis mellitus, chronic obstructive pulmonary disease, dry cough. were all more common in M pneumoniae pneumonia.138 [III] c Legionella pneumophila: younger patients, smokers, absence Where C pneumoniae was the only pathogen identified, the of comorbidity, diarrhoea, neurological symptoms, more illness was generally mild with non-specific symptoms.139 [II] severe infection and evidence of multisystem involvement (eg, abnormal liver function tests, elevated serum creatine kinase). c Mycoplasma pneumoniae: younger patients, prior antibiotics, Coxiella burnetii less multisystem involvement. CAP due to C burnetii (Q fever) causes non-specific clinical c Chlamydophila pneumoniae: longer duration of symptoms features.140 141 [II] Two reviews of Q fever have reported that before hospital admission, headache. infection was more common in younger men and that patients c Coxiella burnetii: males, dry cough, high fever. tended to present with dry cough and high fever.142 143 [III] Epidemiological features are discussed in Section 3. iii16 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

Klebsiella pneumoniae SECTION 5 RADIOLOGICAL, GENERAL AND MICROBIOLOGICAL Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from When compared with S pneumoniae, K pneumoniae was found to INVESTIGATIONS affect men more commonly and to present with a lower platelet 5.1 When should a chest radiograph be performed in the count and leucopenia. Alcoholics were at particular risk of community for patients presenting with suspected CAP? 144 [III] bacteraemic and fatal Klebsiella pneumonia. In UK practice, most CAP is managed in primary care where access to rapid chest radiography is limited. In this setting, Some rarer community respiratory pathogens clinicians have to identify the 5–12% with CAP from the CAP caused by Acinetobacter is seen more often in older patients majority with acute non-pneumonic lower respiratory tract with a history of alcoholism and has a high mortality.145 [III] infections or other diagnoses.324[Ib] This challenge is particularly CAP due to Streptococcus milleri may indicate a dental or difficult in the presence of comorbid illnesses such as left abdominal source of infection.146 [III] CAP due to viridans ventricular failure, chronic lung disease or COPD and in the streptococci is associated with aspiration.147 [III] elderly who frequently present with non-specific symptoms and an absence of chest signs.148 [II] No individual clinical symptom or sign is useful in discrimi- 4.3 CAP in elderly patients: are risk factors and clinical features nating CAP from other acute lower respiratory tract infec- different? tions,159 160 [Ia] and there is poor interobserver reliability in The classic symptoms and signs of pneumonia are less likely in eliciting respiratory signs.161 [II] elderly patients and non-specific features, especially confusion, Woodhead et al23 [II] found that 39% of adults treated with 73 148–150 [II] are more likely. Comorbid illness occurs more antibiotics for an acute lower respiratory tract infection frequently in older patients with CAP and two studies have associated with new focal signs on chest examination had found the absence of fever to be more common than in younger evidence of CAP on chest radiograph compared with 2% of 128 151 [II] patients with CAP. patients who did not have new focal chest signs. By contrast, There is a high incidence of aspiration in elderly patients who Melbye et al162 [II] found that respiratory symptoms and signs 152 present with CAP compared with controls (71% versus 10%). were of only minor value in differentiating patients with Case-controlled studies of pneumonia acquired in nursing radiographic pneumonia in a study of 71 patients suspected by homes have shown that both aspiration and pre-existing their general practitioners of having CAP. The clinical findings comorbid illnesses were more common in nursing home- reported by the general practitioners to be most suggestive to 77 148 [II] acquired pneumonia than in others with CAP. The in- them of CAP (typical history of cough, fever, dyspnoea and patient mortality rate for nursing home-acquired pneumonia chest pains and lung crackles on examination) had low was higher than that for age matched patients with non-nursing predictive values; only a short duration of symptoms (,24 h) 153 [II] home-acquired pneumonia. The relationship between was of significant predictive value. aetiology of CAP and the age of the patient is discussed in Various prediction rules have been published for the diagnosis Section 3. of CAP, [II] but generally have shown the need for confirmatory radiographic evidence. Statistical modelling was used by Diehr et Summary al163 [II] to predict the presence of CAP in 1819 adults presenting http://thorax.bmj.com/ to hospital outpatients with acute cough, 2.6% of whom had c Elderly patients with CAP more frequently present with . non-specific symptoms and have comorbid disease and a CAP on the chest radiograph. The presence of fever ( 37.8uC), higher mortality, and are less likely to have a fever than raised respiratory rate (.25 breaths/min), sputum production younger patients. [II] throughout the day, myalgia and night sweats, and absence of sore throat and rhinorrhoea were the only clinical features that c Aspiration is a risk factor for CAP in elderly patients, predicted CAP when included in a diagnostic rule which had particularly nursing home residents. [II] 91% sensitivity and 40% specificity. Conversely, a number of studies have suggested that CAP can on October 1, 2021 by guest. Protected copyright. 4.4 Aspiration pneumonia be safely ruled out in the absence of abnormal vital signs.159 160 [Ia] Aspiration pneumonia embodies the concept of an infectious One study compared 350 adults presenting with acute pneumonic process consequent upon the aspiration of colonised respiratory symptoms to outpatient clinics and the emergency oropharyngeal or gastric contents. However, in practice, such department in California where CAP had been diagnosed on the causal linkage is seldom verified. Instead, the term ‘‘aspiration chest radiograph with an equal number of age-matched pneumonia’’ is commonly applied to situations when a patient controls. The age range of patients was 21–91 years, with an with risk factors for aspiration presents with pneumonia. These average age of 65 years. The presence of either abnormal vital risk factors include altered level of consciousness, neurological signs (fever .38uC, tachycardia .100/min and tachypnoea disorders such as stroke, presence of dysphagia and gastric .20/min) or an abnormal physical examination of the chest disorders such as gastro-oesophageal reflux. When a broad (crackles, decreased breath sounds, dullness to percussion, definition of aspiration pneumonia is applied to pneumonia wheeze) identified patients with radiographically confirmed study cohorts, up to 10% of patients admitted to hospital with CAP with a sensitivity of 95%, negative predictive value of 92% CAP are identified as having aspiration pneumonia.154 [II] This is and specificity of 56%.164 [II] These findings have not been likely to be an overestimate of the incidence of true aspiration validated in the UK. Despite the age range included in this pneumonia. study, the reduced incidence of classical features of pneumonia Studies of the bacteriology of pneumonia in patients with risk and fever with increasing age at presentation (see Section 4.4) factors for aspiration vary widely in relation to inclusion should be borne in mind when applying these results to elderly criteria, patient characteristics and microbiological techniques patients. used.44 72 154–158 [III] [III] [II] [II] [II] [Ib] [Ib] In true community acquired In practice, general practitioners manage the vast majority of aspiration pneumonia, multiple pathogens including anaerobes patients pragmatically at first presentation. The important are likely. decision in patients presenting with a lower respiratory tract

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii17 BTS guidelines

infection, or suspected CAP, is deciding whether to use an Summary Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from antibiotic, which one and how ill the patient is. Labelling the c There are no characteristic features of the chest radiograph illness as pneumonia is less important.165 in CAP that allows a confident prediction of the likely pathogen. [II] Recommendations It is not necessary to perform a chest radiograph in 5.4 What is the role of CT lung scans in CAP? patients with suspected CAP unless: There are few data on the role of high-resolution CT lung scans c The diagnosis is in doubt and a chest radiograph will in CAP. A small study has reported that high-resolution CT help in a differential diagnosis and management of the acute illness. [D] scans may improve the accuracy of diagnosing CAP compared with chest radiography alone.172 [II] Similarly, CT lung scans c Progress following treatment for suspected CAP is not have improved sensitivity compared with standard chest radio- satisfactory at review. [D] graphs in patients with mycoplasma pneumonia.173 [II] CT lung c The patient is considered at risk of underlying lung scans may be useful in subjects where the diagnosis is in pathology such as lung cancer (see Section 5.6). [D] 174 doubt [III] but, in general, there is little role for CT scanning in the usual investigation of CAP. 5.2 When should a chest radiograph be performed in hospital for With regard to aetiology, one study has reported a difference in patients presenting with suspected CAP? CT appearances in 18 patients with CAP due to bacterial infections A chest radiograph is the cornerstone to confirming a diagnosis compared with 14 patients with atypical pathogens.175 [III] of CAP. In patients ill enough to require hospital referral for suspected CAP, a chest radiograph is essential to establishing the Summary diagnosis of CAP or an alternative diagnosis, and therefore in c guiding management decisions. CT scanning currently has no routine role in the investiga- Antibiotic treatment of patients with suspected CAP prior to, tion of CAP. [II] or without, confirmation by chest radiography potentially leads to inappropriate and excessive antibiotic use. 5.5 How quickly do chest radiographs improve after CAP? The committee felt that the Department of Health’s ‘‘4 hour Radiographic changes resolve relatively slowly after CAP and lag from presentation to admission, transfer or discharge’’ target for behind clinical recovery. In one study, complete resolution of patients admitted to emergency departments represented a chest radiographic changes occurred at 2 weeks after initial practice standard that should apply to all patients presenting to presentation in 51% of cases, in 64% by 4 weeks and 73% at hospital (via the emergency department or acute medical unit) 6 weeks.176 Clearance rates were slower in elderly patients, those 15 with suspected CAP. with more than one lobe involved at presentation, smokers and inpatients rather than outpatients. Multivariate analysis Recommendation showed that only age and multilobe involvement were

c All patients admitted to hospital with suspected CAP independently related to rate of clearance. Age was also a major http://thorax.bmj.com/ should have a chest radiograph performed as soon as factor influencing rate of radiographic recovery in the BTS possible to confirm or refute the diagnosis. [D] The multicentre CAP study.6 [Ib] A study of patients over 70 years of objectiveofanyserviceshouldbeforthechest age showed 35%, 60% and 84% radiographic resolution at 3, 6 radiograph to be performed in time for antibiotics to and 12 weeks, respectively.177 [II] C-reactive protein (CRP) levels be administrated within 4 h of presentation to hospital .200 mg/l were also linked to slower radiographic resolution.178 [III] should the diagnosis of CAP be confirmed. When chest radiographs of patients with bacteraemic pneumo- coccal pneumonia were followed, only 13% had cleared at 179 [III] 5.3 Are there characteristic features that enable the clinician to 2 weeks and 41% at 4 weeks. Pneumonias caused by on October 1, 2021 by guest. Protected copyright. predict the likely pathogen from the chest radiograph? atypical pathogens clear more quickly. The clearance rate has been reported to be faster for mycoplasma pneumonia than for There are no characteristic features on the chest radiograph in legionella or pneumococcal pneumonia, which may take CAP that allow confident prediction of the causative organ- 12 weeks or more.166 [III] In a series of patients with C burnetii ism.98 166–168 [III] The lower lobes are affected most commonly, pneumonia, 81% of the chest radiographs had returned to regardless of aetiology. normal within 4 weeks.143 [III] Multilobe involvement169 [II] at presentation and pleural Radiographic deterioration after admission to hospital was effusions were more likely at presentation in bacteraemic more common with legionella (65% of cases) and bacteraemic pneumococcal pneumonia than in non-bacteraemic pneumo- pneumococcal pneumonia (52%) than with non-bacteraemic coccal pneumonia or legionella pneumonia. Homogenous pneumococcal (26%) or mycoplasma pneumonia (25%).166 [III] shadowing was less common in mycoplasma pneumonia than Residual pulmonary shadowing was found in over 25% of cases in the other types. Lymphadenopathy was noted in some cases of legionella and bacteraemic pneumococcal cases. Deterioration of mycoplasma infections but not in the other types of after admission has also been reported in over half of cases of S infection. CAP due to S aureus appears to be more likely to aureus pneumonia.170 [III] Radiographic deterioration after hospi- present with multilobar shadowing, cavitation, pneumatoceles tal admission appears to be commoner in older patients (aged or spontaneous pneumothorax.170 [III] K pneumoniae has been >65 years).151 [II] reported to produce chest radiograph changes with a predilec- tion for upper lobes (especially the right).171 [II] A bulging interlobar fissure and abscess formation with cavitation have Summary also been reported, although the former is probably just a c Radiological resolution often lags behind clinical improve- reflection of an intense inflammatory reaction that can occur in ment from CAP, particularly following legionella and any severe infection such as pneumonia due to S aureus.170 [III] bacteraemic pneumococcal infection. [III] iii18 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

c Pneumonia caused by atypical pathogens clears more 5.7 What general investigations should be done in a patient with Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from quickly than pneumonia caused by bacterial infection. [III] suspected CAP in the community? c Radiological resolution is slower in elderly patients and General investigations are performed to assess severity (see where there is multilobar involvement. [Ib] Section 6), to assess the impact on or to detect the presence of any comorbid disease, to provide some pointer to the particular aetiological agent or group of pathogens, identify complications 5.6 When should the chest radiograph be repeated during and to monitor progress (see Section 9). recovery and what action should be taken if the radiograph has It may be appropriate to perform investigations in selected not returned to normal? patients, especially if there is delayed improvement on review. Repeat chest radiographs are probably often ordered unnecessa- However, no firm recommendations can be offered. It is a rily following CAP.180 [IVa] Although it has become usual practice matter of clinical judgement. to repeat the chest radiograph on hospital discharge and again at ‘‘routine’’ hospital clinic follow-up at around 6 weeks later, Recommendations there is no evidence on which to base a recommendation c General investigations are not necessary for the regarding the value of this practice in patients who have majority of patients with CAP who are managed in otherwise recovered satisfactorily. the community. [C] Pulse oximeters allow for simple The main concern is whether the CAP was a complication of assessment of oxygenation. General practitioners, an underlying condition such as lung cancer. This concern will particularly those working in out-of-hours and emer- depend on a variety of factors such as age, smoking status, pre- gency assessment centres, should consider their use existing conditions such as COPD and the clinical condition of (see Section 7.1). [D] the patient. In a study of 236 adults presenting to their general c Pulse oximetry should be available in all locations practitioner with a clinical diagnosis of CAP, 10 were found to where emergency oxygen is used. [D] have underlying lung cancer on investigation. There was a high frequency of lung cancer in older smokers (6 of 36 (17%) 5.8 What general investigations should be done in patients smokers aged .60 years), suggesting that a chest radiograph admitted to hospital? was particularly indicated in this group of patients with CAP in Apart from the chest radiograph essential for diagnosis, the only the community.23 [II] Studies of CAP in hospital often exclude other simple non-microbiological tests that influence immediate patients found to have lung cancer, making it difficult to assess management are the urea, which informs severity assessment, how frequently lung cancer presents acutely with CAP. In one and oxygen saturation, which affects supportive management study of 162 adults hospitalised with suspected CAP, the and track and trigger systems in accordance with the BTS diagnosis was accepted in only 127, 10 (6%) of the 162 being guideline for emergency oxygen use in adult patients.183 found to have cancer.36 [II] Another study found only 13 (1.3%) In addition, it is normal practice to take blood for a full blood of 1011 patients hospitalised with CAP to have an underlying count, urea and electrolytes, liver function tests and CRP. These lung cancer on investigation.181 [III] Eight of these were detected often help to identify important underlying or associated http://thorax.bmj.com/ on the admission chest radiograph and the others were detected pathologies including renal or hepatic disease and haematolo- because of unsatisfactory clinical recovery. They concluded that gical or metabolic abnormalities. a convalescent radiograph was useful in detecting occult lung A white cell count of .156109/l strongly implicates a cancer only if signs or symptoms persisted after a month or so. bacterial (particularly pneumococcal) aetiology, although lower The practice of performing bronchoscopy in patients counts do not exclude a bacterial cause.184 [III] A white cell count admitted to hospital with CAP prior to hospital discharge has of .206109/l or ,46109/l is an indicator of severity (see Section 182 [III] been investigated. In patients aged .50 years or who were 6). current or ex-smokers, 14% were found to have an abnormality Considering the role of CRP in the diagnosis of CAP, a on October 1, 2021 by guest. Protected copyright. at bronchoscopy (11% had a bronchial carcinoma diagnosed). prospective study performed in Spain reported a 96% specificity for CAP using a threshold CRP level of .100 mg/l.185 [II] Criticisms of this study are the small number of patients in Recommendations one group and the fact that patients with infective exacerba- c The chest radiograph need not be repeated prior to tions of COPD were excluded. Another study showed that a hospital discharge in those who have made a satisfac- raised CRP level on admission is a relatively more sensitive tory clinical recovery from CAP. [D] marker of pneumonia than an elevated temperature or raised c A chest radiograph should be arranged after about white cell count. All patients with CAP had CRP levels .50 mg/l 6 weeks for all those patients who have persistence of and 75% of patients had levels .100 mg/l.186 [II] In the same paper symptoms or physical signs or who are at higher risk it was reported that a CRP level of .100 mg/l helped to of underlying malignancy (especially smokers and distinguish CAP from acute exacerbations of COPD. Another those aged .50 years) whether or not they have been group found that only 5% of patients admitted with CAP had admitted to hospital. [D] CRP levels ,50 mg/l.187 [III] Although not yet widely available, a c Further investigations which may include broncho- bedside finger-prick CRP test has been used to predict CAP in 168 scopy should be considered in patients with persisting patients presenting with acute cough and, at a cut-off of 40 mg/l, signs, symptoms and radiological abnormalities at was found to have a sensitivity of 70% and a specificity of 90% around 6 weeks after completing treatment. [D] independent of any clinical characteristics.188 [II] CRP levels are c It is the responsibility of the hospital team to arrange generally higher in patients who have not received antibiotic the follow-up plan with the patient and the general therapy before admission.186 [II] practitioner for those patients admitted to hospital With regard to predicting the microbial aetiology of CAP, (see Section 7.5). [D] higher CRP levels have been associated with pneumococcal

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii19 BTS guidelines

pneumonia (especially if complicated by bacteraemia) compared pathogens’’ and respiratory viruses with conventional methods Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from with mycoplasma or viral pneumonias,189 [III] and in legionella reported a microbiological diagnosis in 80 patients (76%) using pneumonia compared with all other identified single aetiolo- the real-time PCR compared with 52 patients (49.5%) using gies.190 [II] conventional methods. However, no urine antigen testing for Data relating to CRP as a marker of severity and of treatment either legionella or pneumococcal infection was included in the failure are discussed in Sections 6.2.1 and 7.3, respectively). study, and most of the increase in diagnostic yield obtained was There are a number of studies examining the role of other due to enhanced detection of rhinoviruses and coronaviruses. biomarkers in CAP such as procalcitonin, however these assays Nevertheless, such studies point the way forward for improving are not currently widely available. aetiological diagnosis in CAP. Several studies198–201 [II] [II] [II] [II] have examined the positivity rate of routine microbiological investigations (blood and Summary sputum cultures) for patients with CAP. These studies provide c The published evidence to date suggests that measurement further evidence that the overall sensitivity of such tests in CAP of CRP on admission may be helpful in distinguishing is low, particularly for patients with low severity CAP and no pneumonia from other acute respiratory illnesses. [III] comorbid disease, and for those who have received anti- biotic therapy prior to admission. One study200 demonstrated Recommendations a direct correlation between the severity of pneumonia (using All patients should have the following tests performed on the Fine Pneumonia Severity Index (PSI)) and blood culture admission: positivity rate, and questioned the value of routine c Oxygenation saturations and, where necessary, arter- blood cultures for patients in PSI risk classes I–III (ie, low ial blood gases in accordance with the BTS guideline severity). However, another study found poor correlation of for emergency oxygen use in adult patients. [B+] blood culture positivity with the PSI among patients hospita- 201 [II] c Chest radiograph to allow accurate diagnosis. [B+] lised with CAP. c Urea and electrolytes to inform severity assessment. [B+] Recommendations c CRP to aid diagnosis and as a baseline measure. [B+] c Microbiological tests should be performed on all c Full blood count. [B2] patients with moderate and high severity CAP, the c Liver function tests. [D] extent of investigation in these patients being guided by severity. [D] c For patients with low severity CAP the extent of 5.9 Why are microbiological investigations performed in patients microbiological investigations should be guided by with CAP? clinical factors (age, comorbid illness, severity indica- Establishing the microbial cause of CAP is useful for several tors), epidemiological factors and prior antibiotic reasons: therapy. [A2] http://thorax.bmj.com/ c Identification of pathogens and antibiotic sensitivity pat- c Where there is clear microbiological evidence of a terns permits selection of optimal antibiotic regimens. To specific pathogen, empirical antibiotics should be date there has been a habit to continue broad-spectrum changed to the appropriate pathogen-focused agent empirical antibiotics even if a specific pathogen has been unless there are legitimate concerns about dual patho- identified. However, with the increasing problem of anti- gen infection. [D] biotic resistance and HCAIs such as C difficile infection, the balance has now swung towards focusing down antibiotic 5.10 What microbiological investigations should be performed in therapy whenever possible.

patients with suspected CAP in the community? on October 1, 2021 by guest. Protected copyright. c Targeted and narrow-spectrum antibiotic therapy limits Comments about the pros and cons of different microbiological drug costs, the threat of antibiotic resistance and adverse investigations are given below in Section 5.11. Many of these drug reactions such as C difficile-associated diarrhoea. investigations will not be appropriate for patients with CAP c Specific pathogens have public health or infection control managed in the community. Such patients are not usually significance, including legionella, psittacosis, C burnetii, severely ill, are at low risk of death and delays in transport of influenza A and multiresistant organisms. Patients with these specimens to the laboratory reduces the yield of bacterial infections should be identified quickly so that appropriate pathogens (especially S pneumoniae) from sputum cultures. treatment and control measures can be implemented. Results are often received too late by the general practitioner to c Microbiological investigations allow monitoring of the be of much practical value in initial management. spectrum of pathogens causing CAP over time. This allows trends regarding aetiology and antibiotic sensitivity to be tracked for public health needs. Recommendations Unfortunately, microbiological investigations are insensitive c For patients managed in the community, microbiologi- and often do not contribute to initial patient management.191 [III] cal investigations are not recommended routinely. [D] In detailed prospective aetiology studies the microbial cause is c Examination of sputum should be considered for not found in 25–60% of patients,23 192 [II] [II] and the yield is even patients who do not respond to empirical antibiotic lower in routine hospital practice.193 194 [III] [III] More recent therapy. [D] studies including the use of PCR and antigen detection c Examination of sputum for Mycobacterium tuberculosis techniques have not generally increased the proportion of should be considered for patients with a persistent patients with a specific aetiological diagnosis.195 196 [II] [II] In productive cough, especially if malaise, weight loss or contrast, one recent prospective study of 105 adults with CAP197 night sweats, or risk factors for tuberculosis (eg, ethnic [II] comparing a multiplex real-time PCR for a range of ‘‘atypical origin, social deprivation, elderly) are present. [D] iii20 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

Table 4 Recommendations for the microbiological investigation of community acquired pneumonia (CAP) Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from Pneumonia severity (based on clinical judgement supported by severity scoring tool) Treatment site Preferred microbiological tests

Low severity Home None routinely. (eg, CURB65 = 0–1 or CRB-65 score = 0, ,3% mortality) PCR, urine antigen or serological investigations* may be considered during outbreaks (eg, Legionnaires’ disease) or epidemic mycoplasma years, or when there is a particular clinical or epidemiological reason. Low severity Hospital None routinely (eg, CURB65 = 0–1, ,3% mortality) but admission PCR, urine antigen or serological investigations* may be considered during outbreaks (eg, indicated for reasons other than pneumonia severity Legionnaires’ disease) or epidemic mycoplasma years, or when there is a particular clinical or (eg, social reasons) epidemiological reason. Moderate severity Hospital Blood cultures (minimum 20 ml) (eg, CURB65 = 2, 9% mortality) Sputum for routine culture and sensitivity tests for those who have not received prior antibiotics (¡Gram stain*) Pneumococcal urine antigen test Pleural fluid, if present, for microscopy, culture and pneumococcal antigen detection PCR or serological investigations* may be considered during mycoplasma years and/or periods of increased respiratory virus activity. Where legionella is suspected", investigations for legionella pneumonia: (a) urine for legionella antigen (b) sputum or other respiratory sample for legionella culture and direct immunofluorescence (if available). If urine antigen positive, ensure respiratory samples for legionella culture

High severity Hospital Blood cultures (minimum 20 ml) (eg, CURB65 = 3–5, 15–40% mortality) Sputum or other respiratory sample{ for routine culture and sensitivity tests (¡Gram stain{) Pleural fluid, if present, for microscopy, culture and pneumococal antigen detection. Pneumococcal urine antigen test Investigations for legionella pneumonia: (a) Urine for legionella antigen (b) Sputum or other respiratory sample{ for legionella culture and direct immunofluorescence (if available)

Investigations for atypical and viral pathogens:** (a) If available, sputum or other respiratory sample for PCR or direct immunofluorescence (or other antigen detection test) for Mycoplasma pneumoniae Chlamydia spp, influenza A and B, parainfluenza 1–3, adenovirus, respiratory syncytial virus, Pneumocystis jirovecii (if at risk) 1 (b) Consider initial and follow-up viral and ‘‘atypical pathogen’’ serology http://thorax.bmj.com/ *If PCR for respiratory viruses and atypical pathogens is readily available or obtainable locally, then this would be preferred to serological investigations. {The routine use of sputum Gram stain is discussed in the text. {Consider obtaining lower respiratory tract samples by more invasive techniques such as bronchoscopy (usually after intubation) or percutanous fine needle aspiration for those who are skilled in this technique. 1The use of paired serology tests for patients with high severity CAP is discussed in the text. If performed, the date of onset of illness should be clearly indicated on the laboratory request form. "Patients with clinical or epidemiological risk factors (travel, occupation, comorbid disease). Investigations should be considered for all patients with CAP during legionella outbreaks. **For patients unresponsive to b-lactam antibiotics or those with a strong suspicion of an ‘‘atypical’’ pathogen on clinical, radiographic or epidemiological grounds. on October 1, 2021 by guest. Protected copyright. c Urine antigen investigations, PCR of upper (eg, nose pneumoniae. Isolation of these bacteria from blood cultures in and throat swabs) or lower (eg, sputum) respiratory patients with CAP is highly specific in determining the tract samples or serological investigations may be microbial aetiology. Bacteraemia is also a marker of illness considered during outbreaks (eg, Legionnaires’ dis- severity. However, many patients with CAP do not have an ease) or epidemic mycoplasma years, or when there is associated bacteraemia. Even in pneumococcal pneumonia the a particular clinical or epidemiological reason. [D] sensitivity of blood cultures is at most only 25%,94 202 [II] [II] and is even lower for patients given antibiotic treatment before 5.11 What microbiological investigations should be performed in admission.129 [II] Several predominantly retrospective North patients admitted to hospital with CAP? American studies and reviews203–206 [II] [III] [III] [III] have questioned The investigations that are recommended for patients admitted the utility of routine blood cultures in patients hospitalised to hospital are summarised in table 4. More extensive with CAP on grounds of low sensitivity, cost and negligible microbiological investigations are recommended only for impact on antimicrobial management. However, despite these patients with moderate or high severity CAP, unless there are limitations, most continue to recommend blood cultures in high particular clinical or epidemiological features that warrant severity CAP. further microbiological studies. Comments and recommenda- tions regarding specific investigations are given below. Recommendations 5.11.1 Blood cultures c Blood cultures are recommended for all patients with Microbial causes of CAP that can be associated with bacter- moderate and high severity CAP, preferably before aemia include S pneumoniae, H influenzae, S aureus and K antibiotic therapy is commenced. [D]

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii21 BTS guidelines

c If a diagnosis of CAP has been definitely confirmed c Can aid the interpretation of culture results and occasionally Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from and a patient has low severity pneumonia with no give an early indication of possible aetiology. comorbid disease, then blood cultures may be omitted. [A2] Disadvantages c Strict criteria for interpretation require appropriate operator 5.11.2 Sputum cultures training. Sputum cultures may identify the causative agent in CAP c Validity of results is directly related to the experience of the including unexpected or antibiotic-resistant pathogens such as S interpreter.213 [II] aureus or antimicrobial-resistant pneumococci. Routine sputum c Sputum Gram stain correlates poorly with culture results in cultures are, however, neither very sensitive nor specific207 [Ia] conditions other than CAP.214 [II] This poses practical and often do not contribute to initial patient management.208 [II] difficulties for laboratories that frequently have to interpret Problems include: results with little or no clinical information. c The inability of patients to produce good specimens. c Lack of availability: a recent survey of diagnostic micro- c Prior exposure to antibiotics. biology laboratories in England and Wales215 [III] revealed c Delays in transport and processing. that, of 138 respondents, 53 laboratories (38%) do not c Difficulty in interpretation due to contamination of the provide a sputum Gram stain service at all and, of the sample by upper respiratory tract flora, which may include remainder, 52 laboratories (38%) do so only on special potential pathogens such as S pneumoniae and ‘‘coliforms’’ request. Thus, ready availability of sputum Gram stain (especially in patients already given antibiotics). cannot be assumed. This lack of availability reflects the opinion of many microbiologists that sputum examination Recommendations is rarely helpful in the diagnosis of CAP. c Sputum samples should be sent for culture and sensitivity tests from patients with CAP of moderate Recommendations severity who are able to expectorate purulent samples c Clinicians should establish with local laboratories the and have not received prior antibiotic therapy. availability or otherwise of sputum Gram stain. Where Specimens should be transported rapidly to the this is available, laboratories should offer a reliable laboratory. [A2] Gram stain for patients with high severity CAP or c Culture of sputum or other lower respiratory tract complications as occasionally this can give an immedi- samples should also be performed for all patients with ate indicator of the likely pathogen. Routine perfor- high severity CAP or those who fail to improve. [A2] mance or reporting of sputum Gram stain on all c Sputum cultures for Legionella spp should always be patients is unnecessary but can aid the laboratory attempted for patients who are legionella urine antigen interpretations of culture results. [B2] positive in order to provide isolates for epidemiologi- c Samples from patients already in receipt of antimicro- cal typing and comparison with isolates from putative bials are rarely helpful in establishing a diagnosis. [B2] http://thorax.bmj.com/ environmental sources. [D] c Laboratories performing sputum Gram stains should adhere to strict and locally agreed criteria for inter- 5.11.3 Sputum Gram stain pretation and reporting of results. [B+] The value of performing a Gram stain on expectorated sputum has been widely debated. A meta-analysis review concluded that 5.11.4 Other tests for Streptococcus pneumoniae the sensitivity and specificity of sputum Gram stain in patients Pneumococcal antigen detection 209 [Ia] with CAP varied substantially in different settings. The Pneumococcal antigens can be detected in various body fluids presence of large numbers of Gram-positive diplococci in during active pneumococcal infection, including sputum, on October 1, 2021 by guest. Protected copyright. purulent samples from patients with CAP can indicate pleural fluid, serum and urine. Antigen detection is less affected 210 [II] pneumococcal pneumonia. A study of 1669 consecutive by prior antibiotic therapy and the detection of antigenaemia adult patients with CAP found that good quality sputum has a correlation with clinical severity.216 [IVb] samples with a predominant bacterial morphotype on Gram A commercial immunochromatographic strip test (BINAX stain (ie, the test was useful) were obtained from only 14.4% of NOW) for detection of pneumococcal antigen in urine has been patients overall and, while Gram-positive diplococci as the introduced in the last few years and been widely taken up. predominant morphotype was highly specific for S pneumoniae, Numerous studies217–222 [II] [II] [II] [II] [II] [III] have evaluated positively no severity subgroup of patients (assessed using the PSI) could the clinical and diagnostic utility and generally good sensitivity 211 [III] be identified in whom the test would be of greater utility. and specificity of the pneumococcal urine antigen test in the 212 [III] A similar study of 347 patients with CAP concluded that diagnosis of pneumococcal pneumonia in adults. The studies Gram stain of sputum was useful in guiding microbiological have shown the usefulness of this assay in determining the diagnosis in just 23% of patients and unreliable in patients who aetiology of CAP, with significantly greater sensitivity rates had received antimicrobial treatment prior to sample collection. than routine blood or sputum cultures. In addition, the test There are many factors which need to be borne in mind when remains positive in 80–90% of patients for up to 7 days after considering the reliability and usefulness of Gram stain results. starting antimicrobial treatment,223 [II] and may also be applied These are summarised below: to other relevant sample types such as pleural fluid.224 [III]

Advantages Pneumococcal PCR c Quick and relatively inexpensive. Many polymerase chain reaction (PCR)-based methods for c Can assess quality of samples (cytological content) with detection of pneumococcal DNA in clinical samples have been rejection of poor quality samples. published, varying in precise methodology and the specific iii22 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

pneumococcal DNA target(s) sought. However, relatively few There are several commercial assays available, including a Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from studies report comprehensive clinical—as opposed to analytical rapid immunochromatographic test. These assays principally sensitivity—evaluations of pneumococcal PCRs in the diagnosis detect infection with L pneumophila serogroup 1. They do not of CAP. One retrospective study225 [III] compared three different reliably detect antigen from other serogroups or legionella PCR methodologies for use on EDTA blood samples from 175 species which can cause infection in immunocompromised bacteraemic patients collected at hospital admission (95 patients who may present with CAP, or recently hospitalised pneumococcal bacteraemia and 80 with bacteraemia due to patients. This has particular significance in nosocomial infec- other organisms). The best sensitivity obtained was 45% versus tion. In one study of culture confirmed cases, while the the gold standard of a positive blood culture for S pneumoniae. sensitivity of commercially available urine antigen tests was The specificity of all three methods was good at 97–100%. The 93.7% for travel-associated cases and 86.5% for community- authors concluded that blood PCR offers no advantage over acquired cases, it was only 45% for nosocomial cases.229 [III] conventional blood culture for pneumococcal diagnosis in bacteraemic patients and is unlikely to be sufficiently sensitive for diagnosis of non-bacteraemic pneumococcal pneumonia. Legionella direct immunofluorescence tests Pneumococcal PCR has also been applied to sputum and other L pneumophila can be detected by direct immunofluorescence respiratory tract samples. However, obtaining a good quality (DIF) on invasive respiratory samples such as bronchial sputum sample, as described above, remains problematic and, aspirates. L pneumophila specific reagents should be used, and more importantly, PCR is not readily able to distinguish not hyperimmune rabbit antisera which are poorly specific. The colonisation from infection of the respiratory tract.226 [III] value of performing DIF on expectorated sputum samples is less Pneumococcal PCR has little to offer for the diagnosis of CAP well established. A considerable degree of laboratory expertise is at this time, being insufficiently sensitive and specific for required for processing and interpretation and, in view of the routine use. widespread availability of urine antigen tests for legionella diagnosis, the use of DIF has declined in recent years in the UK. Recommendations Culture c Pneumococcal urine antigen tests should be performed for all patients with moderate or high severity CAP. The culture of legionella from clinical samples (principally [A2] respiratory samples, including sputum) is very important and c A rapid testing and reporting service for pneumococcal every effort should be made to diagnose by this method. Culture urine antigen should be available to all hospitals is 100% specific and is the only reliable method of detecting admitting patients with CAP. [B+] infection with non-pneumophila legionella species. Culture is also valuable for epidemiological investigations, allowing phenotypic and genotypic comparison of clinical and environ- 5.11.5 Tests for Legionnaires’ disease mental legionella strains. Legionella pneumonia can be severe and carries a significant Problems with culture include: the inability of many patients mortality. Prompt diagnosis is important both for patient http://thorax.bmj.com/ with legionella pneumonia to produce sputum samples; prior management and for public health investigations. Risk factors antibiotic therapy; laboratory time and cost in processing for legionella infection include recent travel (within 10 days of samples; and lack of rapid results (legionella cultures need to onset), certain occupations, recent repair to domestic plumbing be incubated for up to 10 days). Few laboratories will set up systems and immunosuppression. legionella cultures on respiratory samples unless specifically requested to do so. Culture should always be attempted from Urine antigen detection urine antigen positive patients and in suspected nosocomial Detection of L pneumophila urinary antigen by enzyme legionella infection. immunoassay (EIA) is established as a highly specific (.95%) on October 1, 2021 by guest. Protected copyright. and sensitive (,80%) test227 [III] for the detection of infections caused by L pneumophila serogroup 1, the commonest cause of Serology sporadic and travel CAP cases in the UK. Rapid results can be The diagnosis by determination of antibody levels was the obtained at an early stage of the illness, and this is a valuable mainstay of diagnosis of legionella pneumonia in the past. method in the early diagnosis of legionella infection.92 [III] It is Serological assays previously employed in the UK were highly now widely applied in high severity CAP. A recent survey of specific, although false positive results due to a serological cross- diagnostic microbiology laboratories in England and Wales215 [III] reaction may occur in patients with recent Campylobacter revealed that, of 138 respondents, 136 laboratories (99%) offered infection.230 [II] Serological reagents for legionella diagnosis are this test for patients with CAP. no longer available from the Health Protection Agency. Their One study looked at the value of rapid legionella urine place has been filled by a number of commercially available antigen testing in a large outbreak of Legionnaires’ disease serological assays of varying sensitivity and specificity. It is caused by L pneumophila serogroup 1 in Holland.228 [III] This currently recommended that, where a diagnosis of legionella showed a higher test positivity rate for patients with severe infection relies solely on the results of serological testing, the legionella infection. The authors also demonstrated that the sample should be referred to a reference laboratory for results of rapid testing could be used to start early legionella confirmation. appropriate antibiotic management resulting in an improved outcome, as shown by reducing both mortality and the need for intensive care. In another prospective study of sporadic CAP in PCR adults, the early detection of urine legionella antigen positively Detection of legionella DNA by PCR from respiratory samples is influenced the management of seven of nine patients in whom still only available as a reference laboratory or research tool, it was detected.37 [Ib] although it is becoming more widely available.

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii23 BTS guidelines

Recommendations positive, suggesting that serum PCR as opposed to respiratory Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from c Investigations for legionella pneumonia are recom- tract sample PCR—with inherent issues of specimen quality—is mended for all patients with high severity CAP, for worthy of further consideration. PCR diagnosis is already other patients with specific risk factors and for all available in some centres in the UK, will become increasingly patients with CAP during outbreaks. [D] available, and is likely to replace serodiagnosis in the longer c Legionella urine antigen tests should be performed for term. all patients with high severity CAP. [B+] c A rapid testing and reporting service for legionella Recommendations urine antigen should be available to all hospitals c Where available, PCR of respiratory tract samples such admitting patients with CAP. [B+] as sputum should be the method of choice for the c As the culture of legionella is very important for diagnosis of mycoplasma pneumonia. [D] clinical reasons and source identification, specimens of c In the absence of a sputum or lower respiratory tract respiratory secretions, including sputum, should be sample, and where mycoplasma pneumonia is sus- sent from patients with high severity CAP or where pected on clinical and epidemiological grounds, a Legionnaires’ disease is suspected on epidemiological throat swab for Mycoplasma pneumoniae PCR is or clinical grounds. [D] The clinician should specifi- recommended. [D] cally request legionella culture on laboratory request c Serology with the complement fixation test and a forms. range of other assays is widely available, although c Legionella cultures should be routinely performed on considerable caution is required in interpretation of invasive respiratory samples (eg, obtained by broncho- results. [C] scopy) from patients with CAP. [D] c For all patients who are legionella urine antigen 5.11.7 Tests for Chlamydophila species positive, clinicians should send respiratory specimens such as sputum and request legionella culture. [D] Culture This is to aid outbreak and source investigation with It is not appropriate for routine diagnostic laboratories to the aim of preventing further cases. attempt culture of Chlamydophila from respiratory samples from patients with CAP as special laboratory precautions are C psittaci 5.11.6 Tests for Mycoplasma pneumoniae required. ( is a ‘‘category 3 pathogen’’ indicating a high-risk pathogen that may put laboratory staff at risk of The mainstay of conventional diagnosis at the present time is serious illness if infected occupationally.) C pneumoniae is very by serology, although diagnosis by specific PCR is likely to difficult to grow in the laboratory—culture is slow, time- become increasingly available. Culture of M pneumoniae is consuming, expensive and insensitive. generally not available in diagnostic laboratories. The commonest serological assay used historically was the complement fixation test (CFT), but there are various Antigen detection alternative assays such as microparticle agglutination and Chlamydophila antigen can be detected in respiratory samples http://thorax.bmj.com/ EIAs. The CFT is still regarded as the ‘‘gold standard’’ to which using DIF with species- and genus-specific monoclonal anti- 234 [II] other assays have been compared, although it does lack bodies. Species-specific reagents are not available for C sensitivity and specificity. A comparison of various mycoplasma psittaci, which is antigenically highly diverse. DIF requires antibody assays (including IgM and CFT tests) concluded that expertise in slide preparation and reading, and is not widely there is no single assay with significantly better sensitivity and available in diagnostic laboratories. C pneumoniae can also be specificity than the others.231 [III] Elevated CFT titres are usually detected by DIF on throat swabs, with a comparable sensitivity 235 detected no earlier than 10–14 days after the onset of to sputum. However, antigen may be detected for several mycoplasma infection, but the insidious onset and slow months after ‘‘acute’’ infection, making interpretation difficult. on October 1, 2021 by guest. Protected copyright. progression of symptoms means that many patients admitted Chlamydophila antigen can also be detected in respiratory 236 to hospital with mycoplasma CAP have elevated titres on or samples by EIA with comparable sensitivity to PCR, but this shortly after admission. approach requires further studies. One study232 [II] compared 12 commercially available sero- diagnostic assays for M pneumoniae with the CFT using serum Serology samples from patients with PCR-confirmed M pneumoniae Various serological assays are used in the diagnosis of infection and known onset dates. There were wide variations respiratory Chlamydophila infections. The CFT is available in between the tests in sensitivity and specificity, CFT being the some diagnostic serology laboratories. Micro-immunofluores- most specific (97%) although not especially sensitive (65%). The cence (MIF) and whole-cell immunofluorescence (WHIF) are authors concluded that there are currently few commercial specialised reference tests. Several EIAs have been described, and serological assays for the detection of M pneumoniae infections at least one is commercially available in the UK. Each of these with appropriate performances in terms of sensitivity and assays has advantages and disadvantages, and there are specificity, and that PCR is likely to become increasingly particular problems in the serological diagnosis of C pneumoniae important in specific diagnosis. In one series of patients with infections. CAP,197 [II] application of PCR to respiratory tract samples The CFT uses a genus-specific antigen and is relatively doubled the detection rate of M pneumoniae infection versus sensitive and specific for diagnosing psittacosis. However in serological testing alone from 5 to 10 of the 105 patients adults, most infections with C pneumoniae are re-infections and studied. Another study233 [III] described the application of real- these generate only a weak or absent CFT response. time PCR to acute phase serum samples from patients with The MIF and WHIF tests require considerable experience to serologically (CFT) diagnosed mycoplasma pneumonia. Serum read and interpret. They can detect a species-specific response, samples from 15 of 29 patients (52%) were M pneumoniae PCR although this may be delayed for 4–6 weeks, especially with C iii24 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

pneumoniae re-infections. They may also miss C psittaci indicated on all serological request forms so that serum samples Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from infections, depending on the particular serovars included in taken more than 1 week into the illness can be tested the test, and there are conflicting reports regarding the accuracy immediately. of these tests in reliably distinguishing chlamydial species.237 [IVb] A suggested algorithm for performing serological investiga- A commercial EIA has been used with success,238 [III] but has tions is shown in fig 6. not been shown to be significantly superior to CFT.

Molecular techniques Recommendations Amplification of Chlamydophila DNA by PCR using genus- or c Where PCR for respiratory viruses and atypical species-specific primers has been reported from a variety of pathogens is readily available or obtainable locally, respiratory samples. These molecular techniques for diagnosis of this is preferred to serological investigations. [D] respiratory Chlamydophila infection are mostly confined to c Where available, paired serology tests can be consid- research/reference/specialist laboratories at the present time ered for patients with high severity CAP where no although, as with all molecular diagnostics, such tests are likely particular microbiological diagnosis has been made by to become increasingly available, often in commercial kit other means (eg, culture, urine antigen, PCR) and who formats. fail to improve, and/or where there are particular epidemiological risk factors. [D] The date of onset of Recommendations symptoms should be clearly indicated on all serological request forms. [D] c Chlamydophila antigen and/or PCR detection tests c should be available for invasive respiratory samples Serological tests may be extended to all patients from patients with high severity CAP or where there is admitted to hospital with CAP during outbreaks and a strong suspicion of psittacosis. [D] when needed for the purposes of surveillance. The criteria for performing serology tests in these circum- c The complement fixation test remains the most stances should be agreed locally between clinicians, suitable and practical serological assay for routine laboratories and public health. [D] diagnosis of respiratory Chlamydophila infections. [B2] There is no currently available serological test that can reliably detect acute infection due to C SECTION 6 SEVERITY ASSESSMENT pneumoniae. 6.1 Why is severity assessment important? CAP presents to physicians both in primary and secondary care as a wide spectrum of illness from mild and self-limiting to life- 5.11.8 PCR and serology for other respiratory pathogens threatening and occasionally fatal disease. This breadth of PCR tests for a range of respiratory viruses and some atypical illness severity is reflected in the variable mortality rates pathogens are becoming increasingly available through virology reported by studies of CAP in different clinical settings. departments across the UK. The ready availability and extent of The decision regarding the most appropriate site of care, these investigations varies between individual laboratories and including whether hospitalisation of a patient with CAP is http://thorax.bmj.com/ departments, although they are expected to increase over the warranted, is the first and single most important decision in the foreseeable future. Where available, PCR tests are an extremely overall management of CAP. It has consequences both on the useful addition to the diagnostic armamentarium and have the level of treatment received by the patient as well as the overall advantage of being rapid (relevant on occasions for both clinical costs of treatment.30 [III] This decision is best informed by an and infection control purposes) and sensitive, and so are to be accurate assessment of the severity of illness at presentation and preferred over serological tests. Evidence of influenza and/or the likely prognosis. The recognition of patients at low risk of other respiratory virus infections as a cause of primary viral complications—and therefore suitable for treatment out of pneumonia or as a copathogen in bacterial CAP is best sought hospital—has the potential to reduce inappropriate hospitalisa- on October 1, 2021 by guest. Protected copyright. by PCR of nose and throat swabs submitted in virus transport tion and consequently inherent morbidity and costs. medium. When hospital admission is required, further management is At present there are no readily available alternatives to also influenced by illness severity. This includes the extent of serology for some of the atypical pathogens and, according to microbiological investigation, the choice of initial empirical clinical and epidemiological parameters, serological investiga- antimicrobial agents, route of administration, duration of tions may be appropriate. treatment and level of nursing and medical care. Early Respiratory serology usually comprises antibody tests for the identification of patients at high risk of death allows initiation atypical pathogens (M pneumoniae, Chlamydophila spp, C of appropriate antibiotic therapy and admission to an intensive burnetii), influenza A virus, influenza B virus, adenovirus, care setting where assisted ventilation can be readily initiated if respiratory syncytial virus and L pneumophila. Fewer laboratories necessary. rely on CFTs, which are time consuming and inconvenient to perform and have poor sensitivity and specificity. There is little value in testing single serum samples taken 6.2 What clinical factors and investigations are associated with within 7 days of the onset of CAP. Such samples can be stored a poor prognosis on univariate and multivariate analysis? until the follow-up (convalescent) sample is taken (7210 days A large number of studies conducted in hospital and intensive later) and the paired samples tested in parallel. care settings have employed univariate analysis to identify risk However, raised antibody titres—particularly to L pneumo- factors associated with a poor prognosis. In-hospital mortality phila or M pneumoniae—may be found in some patients on or has been the most common outcome measure. Some studies soon after hospital admission, particularly if the onset of have used admission to the ICU as the main outcome symptoms is more than 7 days prior to admission. It is thus measure.239 [Ib] However, differences in ICU admission criteria important that the date of onset of symptoms is clearly make it difficult to compare results from these studies. This is

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii25 BTS guidelines

The lack of pyrexia, which is easily overlooked in clinical Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from practice, has been identified as an important poor prognostic factor in some studies of elderly patients.69 129 253 [II] [Ib] [II] Being previously bed-ridden and having been admitted from a nursing home are other poor prognostic factors that may be inter- related.5 129 153 247 [Ib] [Ib] [II] [Ib]

6.2.1 Biomarkers and inflammatory markers A number of biomarker tests have been demonstrated on univariate and multivariate analyses to be independent prog- nostic factors for either 30-day or in-hospital mortality. These include procalcitonin,261–265 [II] [II] [Ib] [Ib] [II] triggering receptor expressed on myeloid cells-1 (TREM-1),266 [Ib] CD14,267 [Ib] pro- adrenomedullin,268 [Ib] CRP,257 269 [Ib] [II] pro-atrial natriuretic peptide270 271 [Ib] [III] and pro-vasopressin.270 [Ib] Further validation studies are required in most instances. Furthermore, determina- tion of the majority of these biomarkers is not widely or routinely available at present. Of the commonly available tests, one study has reported an association of a low CRP level of ,100 mg/l at the time of hospital admission with reduced risk for 30-day mortality, need for mechanical ventilation and/or inotropic support, and complicated pneumonia.257 [Ib] This observation warrants further evaluation as a number of other studies have not found an association of admission CRP level with prognosis.261 264 265 272 [II] [Ib] [II] [Ib] The level of D-dimers on admission has also been reported to be an independent prognostic marker.273 274 [Ib] [II] However, the clinical value of D-dimers over and above a clinical predictive model has not been established. Moreover, since D-dimers are mainly used in the diagnostic investigation of patients with suspected venous thromboembolism, introducing D-dimers solely as a prognostic marker in CAP will potentially lead to

increased diagnostic uncertainty or confusion which, in turn, http://thorax.bmj.com/ may result in delayed diagnosis or inappropriate management.

Figure 6 Suggested algorithm for serological testing for patients with 6.3 What predictive models for assessing severity on or shortly high severity community acquired pneumonia (CAP). after hospital admission have been tested? Clinical assessment of disease severity is dependent on the experience of the attending clinician, but such clinical judge- ment has been shown to result in apparent underestimation of reflected in the widely varying rates of admission of patients severity.241 [Ib] No single prognostic factor of mortality is on October 1, 2021 by guest. Protected copyright. with CAP to ICU reported, ranging from 1–3% in New Zealand adequately specific and sensitive, so various severity scoring to 5% in the UK, 12–18% in the USA and 35% in systems and predictive models have been developed in an Germany.5 6 239–242 [Ib] [Ib] [III] [II] [Ib] [III] In this document we have attempt to help the clinician identify patients with pneumonia concentrated only on studies that have used mortality as the and a poor prognosis at an early stage. main outcome measure. However, predictive models have recognised limitations. First, Univariate studies have suggested that over 40 different no predictive model enables the unequivocal categorisation of parameters are associated with mortality. An independent patients into definite risk groups, and it is unrealistic to expect association of only a few of these risk factors with mortality this.275 276 [IVb] [IVb] A predictive model is therefore not a substitute has been consistently demonstrated by studies employing for clinical judgement, but should be considered as an adjunct to multivariate analysis. In particular, the following features are clinical judgement. Second, the value of severity-based practice associated with an increased risk of mortality: increasing guidelines in improving clinical outcomes has not yet been fully age;5 6 241 243–247 [Ib] [Ib] [Ib] [Ia] [Ib] [Ib] [III] [Ib] the presence of co-existing established.103 277 278 [III] [II] [II] Data demonstrating that severity- illnesses;5 243–245 247–251 [Ib] [III] [Ib] [Ib] [Ib] [III] [II] [III] [III] raised respiratory based practice guidelines are useful in increasing the proportion rate;5 6 129 241–243 251–254 [Ib] [Ib] [Ib] [Ib] [III] [Ia] [Ib] [Ib] [II] [III] mental of patients managed as ambulatory outpatients without confusion;6 129 244 246 253 255 [Ib] [Ib] [III] [III] [II] [Ib] low blood increasing morbidity or mortality have come from a cluster pressure;6 69 127 129 241 243 246 249 251 253 256 257 [Ib] [II] [III] [Ib] [Ib] [Ia] [III] [II] randomised trial, two large prospective observational studies [III] [II] [II] [Ib] hypoxaemia;33 241 [II] [Ib] respiratory failure;5 33 44 258 [Ib] and before-after implementation studies.279–282 [II] [Ib] [II] [III] [II] [II] [Ib] high or low white cell count;6 243 [Ib] [Ia] bilateral or Whether these benefits were mainly due to the use of a progressive chest radiograph changes;5 33 129 187 243 253 256 258 259 [Ib] [II] predictive model and therefore better stratification of patients [Ib] [III] [Ia] [II] [II] [III,Ib] [Ib] and a positive blood cul- to different management strategies, or simply due to better ture.5 33 36 44 243 250 258 260 [Ib] [II] [II] [II] [Ia] [III] [Ib] [III] implementation of practice guidelines for the management of iii26 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

CAP283 [II] is difficult to differentiate. These encouraging results studies, the CRB65 score was reported to be of similar Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from need confirmation in a wider setting, including the UK. discriminatory value to the CURB65 score.286 298 [II] [Ib] In prospective studies reporting from the UK, 41–45% of patients Conclusions regarding predictive models hospitalised with CAP had CURB65 scores of 0–1, 25–28% had a CURB65 score of 2 and 29–34% had CURB65 scores of 3 or c No predictive model allows the unequivocal categorisation 255 257 more. of patients into definite risk groups. Other predictive models have been developed, including c Predictive models based on severity are best viewed as useful models to predict admission to intensive care as the primary adjuncts to clinical judgement. outcome, or to predict a composite outcome comprising either c Regular reassessment of severity during the course of mortality or need for intensive care.246 287 291 294 300–303 [III] [Ib] [Ib] [Ib] hospital stay is mandatory if treatment is to be adjusted [II] [III] [Ib] [Ib] Widespread validation of most of these models in appropriately, avoiding the morbidity of overtreatment as different settings or patient cohorts has not yet occurred. well as the complications of undertreatment. Differences between studies in relation to criteria for intensive care admission need to be taken into account when interpreting 6.3.1 Pneumonia-specific predictive models these data. Pneumonia Severity Index (PSI) The most widely studied predictive model in the management 6.3.2 Generic predictive models 251 [Ib] of CAP is the PSI developed in the USA. The PSI is based on Generic predictive models such as the sepsis score or APACHE II 20 variables that are used to derive a score which enables scoring system have also been tested in patients with CAP and patients to be stratified into five risk categories based on 30-day been shown to predict outcome.189 258 297 304 [Ib] [IIb] [II] [IIb] mortality. It was developed to identify patients at low risk of However, general adoption of scoring systems originally mortality who might be suitable for ambulatory outpatient designed for use within an intensive care setting is difficult, care, and it is in this setting that it is best validated. In the time-consuming and likely to be impractical. In addition, original study, mortality rates were 0.1%, 0.6%, 0.9%, 9.3% and pneumonia-specific predictive models have been shown to 27% for risk classes I, II, III, IV and V, respectively. The PSI has outperform generic predictive models such as a modified Early been studied in over 50 000 patients worldwide and performs Warning Score, in the context of CAP.248 289 [III] [II] well. Patients in risk classes I–III are usually at low risk of mortality and therefore suitable for outpatient management. 6.4 What severity assessment strategy is recommended for Due to the emphasis on age in the PSI, underestimation of CAP? severe pneumonia occasionally results. One study reported that We have been keen to recommend one severity assessment up to 40% of patients with CAP who were hospitalised were strategy that is applicable to adults of all ages, simple to assigned to low risk classes based on the PSI,284 [II] and another remember and practical to implement both in the community reported that ICU admission occurred in 27% of patients and in hospital. assigned to PSI risk classes I–III.285 [II] These reports reflect the With these principles in mind, the CURB65 score in importance of clinical judgment in assessing disease severity. http://thorax.bmj.com/ conjunction with clinical judgement is recommended as the initial In clinical practice, the major limitation of the PSI with regard severity assessment strategy in hospitals for CAP. The evidence to its widespread and routine adoption in primary care, base for the CURB65 score is robust and continues to increase, emergency departments or medical admission units is the adding to the strength of the current recommendation. The complexity involved in the calculation of the score. simplified CRB65 score which only relies on clinical factors in conjunction with clinical judgement is recommended as the severity CURB65 score assessment strategy in community or primary care settings for The CURB65 score was developed based on a study of over 1000 CAP. prospectively studied patients with CAP from three countries: on October 1, 2021 by guest. Protected copyright. 255 [Ib] the UK, New Zealand and the Netherlands. The 6-point Summary of the CURB65 score CURB65 score, one point for each of Confusion, Urea . c 7 mmol/l, Respiratory rate >30/min, low systolic Confusion: New mental confusion, defined as an Abbreviated Mental Test score191 [II] (summarised in box 2) (,90 mm Hg) or diastolic ((60 mm Hg) Blood pressure, age of 8 or less. >65 years (CURB65 score) based on information available at c initial hospital assessment, enabled patients to be stratified Urea: Raised .7 mmol/l (for patients being seen in according to increasing risk of mortality (score 0, 0.7%; score 1, hospital). 2.1%; score 2, 9.2%; scores 3–5, 15–40%). A similar pattern of c Respiratory rate: Raised >30/min. increasing disease severity was reported when only clinical c Blood pressure: Low blood pressure (systolic ,90 mm Hg parameters were considered (CRB65) giving a 5-point score (risk and/or diastolic (60 mm Hg). of mortality for each score: score 0, 1.2%; score 1, 5.3%; score 2, c Age >65 years. 12.2%; scores 3–4, up to 33%). Since then, the CURB65 score has been studied in over 12 000 6.4.1 Clinical judgement 257 266 286–295 [Ib] [Ib] [II] [Ib] [Ib] [II] [Ib] [II] [III] [II] [Ib] [III] patients. The results Clinical judgement is essential when deciding on the manage- from all but one of the prospective validation studies indicate ment of all patients with CAP, particularly in the following that the PSI and the CURB65 score perform equally well at three areas with regard to severity assessment: discriminating patients into mortality risk groups. The CRB65 c Interpretation of CURB65 score. Each patient must be score has been specifically studied in over 6000 patients managed individually and the interpretation of the CURB65 representing a mix of patients seen both in the community score is best refined through clinical judgement that takes and in hospitals.255 286 287 289 296–299 [Ib] [II] [Ib] [II] [Ib] [II] [Ib] [II] All studies into account all the clinical information available at the reported findings similar to the derivation study and, in certain time. For instance, the combination of age ,50 years, the

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii27 BTS guidelines

absence of coexisting disease and a CRB65 or CURB65 score and hospital referral and assessment should be con- Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from of 0 identifies patients with a very good prognosis who sidered. [B+] should be suitable for home treatment. In comparison, c Patients who have a CRB65 score of 3 or more are at young patients with a respiratory rate of .40/min may high risk of death and require urgent hospital admis- warrant hospital supervised management despite a CRB65 sion. [B+] or CURB65 score of 1. Clinical judgement is especially c When deciding on home treatment, the patient’s social important in patients at high risk of death (CURB65 scores circumstances and wishes must be taken into account 3, 4 and 5) in whom decisions regarding intravenous in all instances. [D] administration of antibiotics or transfer to critical care facilities need to be made. 6.6 Severity assessment of CAP in patients seen in hospital c Stability of comorbid illnesses. The CURB65 score is The severity assessment of CAP in patients seen in hospital is primarily a CAP severity assessment tool. Pneumonia may shown in fig 8. result in a worsening of comorbid illness that warrants hospital or critical care management irrespective of severity of pneumonia. Recommendations c Social circumstances. The morbidity associated with CAP c For all patients, the CURB65 score should be inter- negatively influences the functional status of patients and preted in conjunction with clinical judgement. [D] therefore the extent that patients may be able to manage at c Patients who have a CURB65 score of 3 or more are at home within a given set of social circumstances. Patient high risk of death. These patients should be reviewed choice should also be considered when determining social by a senior physician at the earliest opportunity to circumstances and the feasibility of further management at refine disease severity assessment and should usually home. be managed as having high severity pneumonia. Patients with CURB65 scores of 4 and 5 should be Recommendations assessed with specific consideration to the need for transfer to a critical care unit (high dependency unit or c Clinical judgement is essential in disease severity intensive care unit). [B+] assessment. [D] c PatientswhohaveaCURB65scoreof2areat c The stability of any comorbid illness and a patient’s moderate risk of death. They should be considered social circumstances should be considered when for short-stay inpatient treatment or hospital-super- assessing disease severity. [D] vised outpatient treatment. [B+] c Patients who have a CURB65 score of 0 or 1 are at low 6.5 Severity assessment of CAP in patients seen in the risk of death. These patients may be suitable for community treatment at home. [B+] The severity assessment of CAP in patients seen in the c When deciding on home treatment, the patient’s social circumstances and wishes must be taken into account community is shown in fig 7. http://thorax.bmj.com/ in all instances. [D] Recommendations 6.7 Reviewing severity status after initial assessment in hospital c For all patients, clinical judgement supported by the Summary CRB65 score should be applied when deciding whether to treat at home or refer to hospital. [D] c Regular and structured clinical review and reassessment of c Patients who have a CRB65 score of 0 are at low risk of disease severity facilitates the stepping down and stepping death and do not normally require hospitalisation for up of antibiotic management. [Ib] on October 1, 2021 by guest. Protected copyright. clinical reasons. [B+] c Patients who have a CRB65 score of 1 or 2 are at Recommendations increased risk of death, particularly with a score of 2, c Regular assessment of disease severity is recom- mended for all patients following hospital admission. The ‘‘post take’’ round by a senior doctor and the Box 2 Abbreviated Mental Test medical team provides one early opportunity for this review. [D] The Abbreviated Mental Test (each question scores 1 mark, total c All patients deemed at high risk of death on admission 10 marks) to hospital should be reviewed medically at least 12- c Age hourly until shown to be improving. [D] c Date of birth c Time (to nearest hour) c Year SECTION 7 GENERAL MANAGEMENT IN THE COMMUNITY AND c Hospital name IN HOSPITAL c Recognition of two persons (eg, doctor, nurse) 7.1 What general management strategy should be offered to c Recall address (eg, 42 West Street) patients treated in the community? c Date of First World War Patients with CAP may present with fever, cough, sputum c Name of monarchs production or pleuritic pain and usually have localised signs on c Count backwards 20 R 1 chest examination. They should be advised to rest and avoid A score of 8 or less has been used to define mental confusion in smoking305 [IIb] and, especially when febrile, be encouraged to the CURB65 severity score. drink plenty of fluids. It is important to relieve pleuritic pain using simple analgesia such as paracetamol or non-steroidal iii28 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

practice for use in the assessment of patients who may have Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from pneumonia and other acute respiratory illnesses. Oxygen saturation below 94% in a patient with CAP is an adverse prognostic feature and also an indication for oxygen therapy,309 [IVb] which will usually require urgent referral to hospital. Patients who fall outside the low severity criteria for CAP should be assessed for the need for hospital referral (see Section 6). Social factors will also play an important part in the decision to refer a patient to hospital. Patients with moderate or high severity pneumonia should be admitted to hospital and managed, where possible, with input from a physician with an interest in respiratory medicine.

Recommendations c Patients with suspected CAP should be advised to rest, to drink plenty of fluids and not to smoke. [D] c Pleuritic pain should be relieved using simple analgesia such as paracetamol. [D] c The need for hospital referral should be assessed using the criteria recommended in section 6. [C] c Pulse oximetry, with appropriate training, should be available to general practitioners and others respon- sible for the assessment of patients in the out-of-hours setting for the assessment of severity and oxygen requirement in patients with CAP and other acute respiratory illnesses. [D]

7.2 What review policy should be adopted in patients managed in the community? When to review a patient with CAP in the community will be determined by the initial severity assessment and other factors such as reliable help in the home. Patients assessed as being at Figure 7 Severity assessment of community acquired pneumonia low severity should improve on appropriate therapy within

(CAP) in patients seen in the community (CRB65 severity score plus 48 h, at which time severity reassessment is recommended. http://thorax.bmj.com/ clinical judgement). DBP, diastolic blood pressure; SBP, systolic blood Those who fail to improve within 48 h should be considered for pressure. hospital admission. Patients who do not fulfil the criteria for low severity and are being managed at home will require more anti-inflammatory drugs. Physiotherapy is of no proven benefit frequent review. in acute pneumonia.306 [III] Nutritional status appears important both to the outcome and the risk of acquiring pneumonia and, in prolonged illness, nutritional supplements may be helpful. Recommendations Patients with pneumonia are often catabolic and those aged c Review of patients in the community with CAP is on October 1, 2021 by guest. Protected copyright. .55 years who are malnourished appear to be at greater risk of recommended after 48 h or earlier if clinically indi- developing pneumonia.150 307 [III] [III] cated. Disease severity assessment should form part of Patients with pneumonia often become hypoxic because the clinical review. [D] pulmonary blood flow takes place through unventilated lung c Those who fail to improve after 48 h of treatment tissue. The clinical signs of hypoxia are non-specific and often should be considered for hospital admission or chest difficult to recognise in the early stages. They include altered radiography. [D] mental state, dyspnoea and tachypnoea. Respiratory rate should therefore always be assessed. Central cyanosis is unreliable both 7.3 What general management strategy should be offered to as a clinical sign and also as an indicator of tissue hypoxia. In patients in hospital? contrast, pulse oximetry which measures arterial oxygen Initial management saturation (SpO2) is, in most situations, a simple and reliable There is some evidence that use of a critical care pathway for method of assessing oxygenation. However, poor peripheral patients referred to hospital can reduce the hospital admission perfusion, jaundice and pigmented skin can produce a falsely of low-risk patients and can also rationalise inpatient manage- low saturation and carboxyhaemoglobin a falsely high satura- ment.310 [Ib] tion. Pulse oximetry is now widely available in North America. All patients referred to hospital with CAP should have a chest A survey of 944 outpatients and 1332 inpatients with evidence radiograph (if not already performed in the community) and of CAP enrolled from five sites in the USA and Canada reported should have oxygenation assessed by pulse oximetry, preferably increasing assessment of arterial oxygen saturation with pulse while breathing air. Those with SpO2 ,94% should have arterial oximetry in up to 58% of outpatients and 85% of inpatients.308 blood gas measurements, as should all patients with features of [II] It is recommended that pulse oximetry, with appropriate high severity pneumonia. Knowledge of the inspired oxygen training, should become more widely available in general concentration is essential to the interpretation of blood gas

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii29 BTS guidelines

Figure 8 Hospital management of Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from community acquired pneumonia (CAP) in the first 4 h. CXR, chest x ray; DBP, diastolic blood pressure; SBP, systolic blood pressure. http://thorax.bmj.com/ on October 1, 2021 by guest. Protected copyright. measurements and should be clearly recorded with the blood gas .6 kPa or 45 mm Hg) and acidotic (pH ,7.35 or [H+] . result. 45 nmol/l), ventilatory support should be considered, especially Continuous oxygen therapy is usually indicated for those if acidosis has persisted for more than 30 min despite appro- 183 patients with arterial oxygen tension (PaO2) ,8 kPa. The aim priate therapy. of oxygen therapy should be to maintain PaO2 >8 kPa or SpO2 Patients admitted with pneumonia should be assessed for 94–98% in patients who are not at risk of hypercapnic volume depletion and may require intravenous fluids. respiratory failure. In nearly all cases of CAP, unless complicated The use of unfractionated or low molecular weight heparins by severe COPD with ventilatory failure, high concentrations of for the prevention of venous thromboembolism in patients with oxygen of 35% or more are indicated and can be safely used. respiratory tract infections has been demonstrated in clinical High concentration oxygen therapy given to patients at risk trials.311–313 [Ia] of hypercapnic respiratory failure, such as patients with A randomised study (n = 458) found early mobilisation moderate or severe COPD, can reduce hypoxic drive and (sitting out of bed for at least 20 min within the first 24 h of increase ventilation-perfusion mismatching. In such patients, hospital admission with increasing mobility on subsequent initial treatment should be with low oxygen concentrations days) decreased length of stay by 1.1 days.314 [Ib] Further studies (24–28%), guided by arterial blood gas measurements, with the are needed. aim of keeping oxygen saturation at 88–92% without causing a Routine airway clearance has not been shown to improve fall in arterial pH (pH ,7.35 or [H+] .45 nmol/l.183 In selected outcome.315 [Ib] cases, non-invasive ventilation or respiratory stimulants may be While chest physiotherapy is of no proven value in acute of value and transfer to a high dependency unit or ICU area pneumonia,315 [III] a single randomised trial using positive should be considered. If the patient is hypercapnic (PaCO2 expiratory pressure has suggested that ‘‘bottle-blowing’’ into iii30 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

an underwater seal bottle on 10 occasions daily can shorten temperature .37.8uC, heart rate .100/min, respiratory rate Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from hospital stay.316 [II] .24/min, systolic blood pressure ,90 mm Hg, oxygen satura- In cases of severe pneumonia requiring prolonged hospital tion ,90%, inability to take oral medication or abnormal admission, increased nutritional support (whether enteral, mental status. Forty-six per cent of those discharged home with parenteral or via nasogastric feeding) should be arranged. two of these unstable factors died or were readmitted within 30 days. In contrast, only 11% of those with no unstable factors died or were readmitted within 30 days.319 [II] A similar Recommendations prospective cohort study in 373 patients found that 22% of c All patients should receive appropriate oxygen therapy patients were discharged with one or more unstable factors, with monitoring of oxygen saturations and inspired which led to increased mortality (14.6% vs 2.1%) and increased 320 [II] oxygen concentration with the aim to maintain PaO2 at readmission within 60 days. >8 kPa and SpO2 94–98%. High concentrations of oxygen can safely be given in patients who are not at Recommendations risk of hypercapnic respiratory failure. [D] c Temperature, respiratory rate, pulse, blood pressure, c Oxygen therapy in patients at risk of hypercapnic mental status, oxygen saturation and inspired oxygen respiratory failure complicated by ventilatory failure concentration should be monitored and recorded should be guided by repeated arterial blood gas initially at least twice daily and more frequently in measurements. [C] those with severe pneumonia or requiring regular c Patients should be assessed for volume depletion and oxygen therapy. [C] may require intravenous fluids. [C] c C-reactive protein should be remeasured and a chest c Prophylaxis of venous thromboembolism with low radiograph repeated in patients who are not progres- molecular weight heparins should be considered for all sing satisfactorily after 3 days of treatment. [B+] patients who are not fully mobile. [A+] c Patients should be reviewed within 24 h of planned c Nutritional support should be given in prolonged discharge home, and those suitable for discharge illness. [C] should not have more than one of the following c Medical condition permitting, patients admitted to characteristics present (unless they represent the usual hospital with uncomplicated CAP should sit out of bed baseline status for that patient): temperature .37.8uC, for at least 20 min within the first 24 h and increase heart rate .100/min, respiratory rate .24/min, sys- mobility each subsequent day of hospitalisation. [A2] tolic blood pressure ,90 mm Hg, oxygen saturation c Patients admitted with uncomplicated pneumonia ,90%, inability to maintain oral intake and abnormal should not be treated with traditional airway clearance mental status. [B+] techniques routinely. [B+] c Patients should be offered advice regarding expectora- 7.4 What advice should be given regarding the critical care tion if there is sputum present. [D] management of CAP? c Airway clearance techniques should be considered if Severity assessment is an important part of hospital manage- http://thorax.bmj.com/ the patient has sputum and difficulty with expectora- ment as it can identify those patients at increased risk of death. tion or in the event of a pre-existing lung condition. Patients who fulfil the severity criteria for high severity CAP on [D] admission and who do not respond rapidly should be considered for transfer to a high dependency unit or a critical care unit (see Section 6). Persisting hypoxia with PaO2 ,8 kPa despite Monitoring in hospital maximal oxygen administration, progressive hypercapnia, Pulse, blood pressure, respiratory rate, temperature, oxygen severe acidosis (pH ,7.26), shock, or depressed consciousness saturation (with a recording of the inspired oxygen concentra- are also indications for transfer to critical care for assisted on October 1, 2021 by guest. Protected copyright. tion at the same time) and mental status should be measured ventilation and cardiovascular support.321 [IVb] initially at least twice daily. Those with high severity Observational studies indicate that non-invasive ventilation pneumonia, requiring continuous oxygen or cardiovascular (NIV) is being used to treat respiratory failure in CAP in many support, should be monitored more frequently. Vital signs critical care units.322 [III] However, a systematic review in 2003 may be captured by an early warning score and can be used to concluded that there was no clear benefit of NIV in acute trigger escalation or de-escalation of management.317 respiratory failure in a non-COPD population.323 [Ia] A further The acute phase reactant CRP is a sensitive marker of systematic review published in 2004 drew broadly similar progress in pneumonia.187 189 [III] [III] Prospective studies have conclusions. This review included all randomised studies of shown that repeat measurement of CRP at day 3 or 4 is helpful patients with acute hypoxaemic respiratory failure given NIV. in identifying patients with treatment failure.257 318 [Ib] A failure This was a very heterogeneous group and included immuno- of CRP to fall by 50% is associated with increased 30-day suppressed patients, those following lung resection and cases of mortality, increased need for mechanical ventilation and/or post-extubation failure. Pooled data suggested a reduced need inotropic support and increased incidence of complicated for intubation with NIV but no effect on mortality once studies pneumonia such as empyema (see Section 6.2.1 and Section including patients with COPD or pulmonary oedema were 9).257 [Ib] excluded.324 [Ia] The number of patients with CAP included in Failure to improve over 4 days is an indication to repeat the these studies has been very limited; only one study exclusively chest radiograph. focused on CAP and even this trial only recruited 33 patients In discharge planning, a US prospective multicentre observa- without COPD.325 [II] tional cohort study of 680 patients admitted to hospital with Continuous positive airways pressure (CPAP) is also used in CAP reported that almost 20% left hospital with one or more some cases of pneumonia. However, a randomised controlled unstable factors in the 24 h prior to discharge. These included trial (RCT) of 123 patients with acute lung injury (61 with

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii31 BTS guidelines

pneumonia) published in 2000 found no reduction in intubation intensive care working in close collaboration with Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from or improved outcome with CPAP.326 [II] In addition, CPAP specialists in respiratory medicine. [D] appeared to delay intubation in some patients with adverse c Neither non-invasive ventilation (NIV) nor continuous consequences. In the non-COPD population with CAP, non- positive airways pressure (CPAP) support is routinely invasive modes of respiratory support are unlikely to be indicated in the management of patients with respira- successful. This is particularly the case in patients developing tory failure due to CAP. [A2] other organ failure. c If a trial of non-invasive support is considered Despite the apparent benefit of activated protein C (APC) in indicated in CAP, it must only be conducted in a patients with severe sepsis shown in the PROWESS study,327 [Ia] critical care area where immediate expertise is avail- there is still substantial controversy about clinical efficacy. The able to enable a rapid transition to invasive ventila- importance of this issue to CAP is highlighted in a retrospective tion. [D] subgroup analysis of outcome in the subgroup of patients with c Steroids are not recommended in the routine treat- CAP in the PROWESS study.328 [II] More than one-third of ment of high severity CAP. [A+] patients recruited were diagnosed as having severe CAP, c Granulocyte colony stimulating factor is not routinely although this did not correspond precisely with the Centre for recommended as an adjunct to antibiotics. [A+] Disease Control definition. Twenty-eight day mortality was reduced in the treatment group (odds ratio (OR) 0.81, 95% CI 7.5 What arrangements should be made for follow-up after 0.67 to 0.93). By day 90, the OR crossed the no-effect line. hospital discharge and by whom? However, the groups were not well matched for important It is usual practice to arrange ‘‘routine’’ hospital clinic follow-up covariables and the improved outcome was only found after and repeat the chest radiograph at around 6 weeks after statistical adjustment. There was also some evidence that discharge. However, there is no evidence on which to base a outcome in the less severe CAP group treated with APC was recommendation regarding the value of this practice in patients worse. A recent systematic review of APC in sepsis concluded who have otherwise recovered satisfactorily. It is also not that there was no definite evidence for efficacy of APC in sepsis, known whether there is any value in arranging clinical follow- but the risk of bleeding was increased.329 [Ia] In view of the up in a hospital clinic rather than with the patient’s general uncertainty, a further multicentre RCT of APC in severe sepsis practitioner. The main concern is whether the CAP was a is being conducted. APC continues to have a European product complication of an underlying condition such as lung cancer licence for the treatment of severe sepsis, including that caused (see Section 5.6). by CAP. No definite treatment recommendation can be given At discharge or at follow-up, patients should be offered access until the results of the new RCT become available. to information about CAP. In one study of 200 patients who One RCT and a systematic review on steroids in severe CAP had recently recovered from CAP, a patient information leaflet have been published since the last guidelines update. The single was judged to be very helpful by the majority of patients.335 [III] RCT enrolled 47 patients to placebo versus 7-day hydrocorti- A patient information leaflet on CAP is available on request sone infusion.330 [II] The trial was stopped early because of from British Lung Foundation Headquarters (British Lung reported efficacy of the steroid treatment. However, the Foundation, Freepost SW1233, London EC1B 1BR) and British http://thorax.bmj.com/ primary end point was gas exchange and mortality was very Lung Foundation UK regional offices. low in both groups. In addition, patients were not well matched (controls were sicker and the steroid group received more NIV). Recommendations The systematic review identified three RCTs of steroids in c Clinical review should be arranged for all patients at 331 [Ia] CAP. All were small underpowered studies (including the around 6 weeks, either with their general practitioner above), which were not optimally conducted. The review or in a hospital clinic. [D] concluded that there was no evidence for the use of steroids c At discharge or at follow-up, patients should be on October 1, 2021 by guest. Protected copyright. in severe CAP. In addition, a recent multicentre RCT of patients offered access to information about CAP such as a with severe sepsis found no survival benefit with hydrocorti- patient information leaflet. [D] 332 [Ib] sone treatment. This was a heterogeneous group, but a c It is the responsibility of the hospital team to arrange significant number had respiratory infections. There is therefore the follow-up plan with the patient and the general no high-grade evidence for the efficacy of steroids in severe CAP. practitioner. [D] Granulocyte colony stimulating factor (G-CSF) has been the Recommendations regarding whether or not to repeat the chest subject of a number of clinical trials in severe infection. A recent radiograph or perform further investigations at follow-up are Cochrane review of 2018 patients with pneumonia revealed that given in Section 5.6. G-CSF, as an adjunct to antibiotics, did not improve 28-day mortality.333 [Ia] SECTION 8 ANTIBIOTIC MANAGEMENT Bronchoscopy after intubation may be valuable to remove retained secretions, to obtain further samples for culture and to 8.1 Introduction exclude endobronchial abnormality such as carcinoma. Antimicrobial chemotherapy is essential to the management of Hospital-acquired ventilator-associated pneumonia can occur CAP. While mild pneumonia may be self-limiting, the timely in approximately 14% of patients mechanically ventilated for use of appropriate antibiotics abbreviates illness, reduces the severe CAP and causes increased mortality.334 [III] Other aspects risk of complications and lowers mortality. of ICU management are outside the scope of these guidelines. Few pneumonias are defined microbiologically at initial assessment and hence most prescribing is empirical, especially when managed in the community. Among hospitalised patients Recommendations the aetiology may be determined, thereby permitting modifica- c Patients with CAP admitted to ICUs should be tion of the initial empirical regimen. However, in practice this managed by specialists with appropriate training in applies to the minority of infections.194 [II] Clinical, epidemiological iii32 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

and radiographic information is rarely predictive of the microbial samples in the UK and Ireland 1999/2000 to 2006/7. They report Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from aetiology. An important principle is that pathogens responsible no convincing evidence of an increase in non-susceptibility over for CAP are diverse and vary in their ability to cause severe time, 94% of bacteraemia isolates and 92% of respiratory isolate disease.243 [Ib] The highest mortality rates are associated with being fully susceptible to penicillin and 85% and 88% of blood and pneumococcal infection and with Legionnaires’ disease. respiratory isolates, respectively, susceptible to erythromycin and, Severity assessment and the association of pre-existing by implication, other macrolides.351 [II] With regard to erythromy- comorbid disease is essential in predicting prognosis and, in cin, resistance is the result of genetic mutations that either affect turn, determines management, choice of antibiotic therapy and thetargetsite(erm gene mutations) or result in elimination of the its method of administration (see Section 6). drug by an efflux pump (mef gene mutation). The distribution of such strains differs internationally and probably explains varia- tion in the clinical impact of such resistance, since erm gene 8.2 Antibiotic stewardship and the individual clinician’s mutations are linked to high level resistance. Tetracyclines are not responsibility to prevent the overuse of antibiotics when widely used in the treatment of CAP and resistance among S managing CAP pneumoniae is relatively low. Likewise, reduced susceptibility of S The choice of antibiotic regimen has consequences beyond the pneumoniae to fluoroquinolones is beginning to be reported, but management of the individual patient. The inappropriate 352 generally remains low in the UK. [II] Recent trends in penicillin, application of CAP guidelines to community acquired lower erythromycin and tetracycline resistance of around 4000–5000 S respiratory tract infections other than pneumonia and hospital pneumoniae isolated from blood and cerebrospinal fluid cultures acquired pneumonia leads, in turn, to inappropriate and each year in England and Wales and reported routinely to the potentially excessive antibiotic use. Too loose an interpretation Health Protection Agency (HPA) are shown in fig 9 (HPA of ‘‘severe pneumonia’’ also contributes to the overprescribing unpublished data). b of macrolides and -lactams, especially when administered Beta-lactamase production among H influenzae varies geogra- parenterally, in the management of hospitalised patients with phically but ranges from 2% to 17% in various parts of the CAP. UK.344 353 [II] [II] Data from the BSAC surveillance programme in Overuse of antibiotics in CAP increases the cost of manage- the UK and Ireland 1999/2000 to 2006/7 suggest that b- ment and, particularly in relation to quinolones and cephalo- lactamase production in H influenzae has been relatively stable sporins, serves as a driver for health care-associated infections, at around 15% over the study period.354 [II] However, this is an 18 336–342 [Ib] [II] [IVa] [II] [II] [Ib] including MRSA and C difficile infection. uncommon cause of pneumonia and, unless local data suggest [Ia] [Ib] The avoidance of inappropriate or excessive use of otherwise, there is insufficient justification to include a b- antibiotics is specifically discussed in Section 8.18. Proper lactamase resistant antibiotic regimen in initial empirical patient selection for treatment and the correct use of therapy of low or moderate severity CAP. M catarrhalis is an antimicrobial agents are emphasised in this document. even rarer cause of CAP, for which the same argument applies. In particular, these guidelines stress that the use of empirical S aureus is widely resistant to penicillin,355 [II] and an broad-spectrum antibiotics is initially recommended only in increasing number are now methicillin-resistant (MRSA). patients with high severity CAP. This group of patients When occurring in the community within the UK, this http://thorax.bmj.com/ comprise approximately one-third of all patients admitted to generally reflects hospitalisation within the recent past or hospital with confirmed CAP. Regular review and the prompt residence within a nursing home. Hence, b-lactamase unstable ‘‘de-escalation’’ to narrow-spectrum antibiotics based on early penicillins (penicillin G, aminopenicillins) and, in the case of microbiological investigations are also emphasised. MRSA, isoxazolyl penicillins (flucloxacillin, cloxacillin) and cephalosporins are inappropriate for such infections. 8.3 Antibiotic resistance of respiratory pathogens L pneumophila and Legionella spp in general remain susceptible The rate of increase in resistance among respiratory pathogens to fluoroquinolones, macrolides and rifampicin, although in has tended to level off in recent years. vitro low level resistance has been found in some isolates. on October 1, 2021 by guest. Protected copyright. Antibiotic resistance among S pneumoniae is the main concern However, the clinical significance of these observations remains 356 owing to the dominance of this organism as a cause of CAP and unclear. because penicillin and macrolide resistance are frequently linked.343 344 [II] [II] Resistance among pneumococci is the result 8.4 Newer antibiotics of alterations in one or more of the penicillin-binding proteins, Since the 2001 guidelines were published, moxifloxacin has been thus reducing their affinity for penicillin. This in turn leads to a licensed in the UK for the treatment of ‘‘non-severe CAP’’. It is requirement for higher drug concentrations to bring about death not licensed at this time for ‘‘severe CAP’’, nor is an intravenous of the organism. Of the .90 known pneumococcal serotypes, a preparation available in the UK; hence, we have not assessed small number have been responsible for penicillin resistance studies which have used intravenous moxifloxacin. worldwide, among which selected clones (eg, 23F, 9V and 6B) There are reported microbiological, pharmacokinetic and have become widely disseminated. However, despite these pharmacodynamic advantages for moxifloxacin compared with concerns, the clinical importance of in vitro penicillin resistance levofloxacin.357 358 [II] Clinical studies have generally shown among S pneumoniae remains uncertain when treating pneumo- equivalence with other oral antibiotics used for CAP.359–361 [Ib] coccal pneumonia.345–350 [II] [II] [IVb] [IVa] [II] [II] This is reflected in the [Ib] [Ib] One showed similar outcomes but fewer side effects when continued ability of current doses of penicillins to inhibit strains compared with oral amoxycillin (1 g tds) and/or clarithro- of intermediate susceptibility (minimum inhibitory concentra- mycin.362 [Ib] However, mainly in view of the increased risk of tion (MIC) of penicillin 0.1–1.0 mg/l), as well as many strains adverse hepatic reactions associated with moxifloxacin, the exhibiting higher level resistance (as defined by an MIC .1 mg/l). European Medicines Agency recommended in July 2008 that The British Society of Antimicrobial Chemoptherapy (BSAC) moxifloxacin should only be given in CAP when treatment with surveillance project has reported on pneumococcal susceptibility other antibiotics cannot be used. Similar advice is given in the to various antimicrobials from both blood and respiratory tract British National Formulary (http://www.bnf.org/bnf/).363

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii33 BTS guidelines

Figure 9 Resistance (%) to penicillin Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from (high and intermediate), erythromycin and tetracycline among selected Streptococcus pneumoniae (blood and cerebrospinal fluid) isolates from laboratories reporting to the Public Health Laboratory Service.

8.5 Clinical studies of management and international differences the many key questions that will enable the management of in recommendations CAP to be placed on a sounder basis. The responsibility for this In defining the UK choice of empirical and specific therapy for presents a challenge to medical practitioners, healthcare CAP, it is apparent that the international differences in systems, grant-giving bodies and industry. We have also only published recommendations cannot be entirely based on considered antibiotics licensed and available in the UK at the geographical variation in the distribution and antibiotic time we prepared these guidelines. susceptibility of pathogens responsible for CAP. There is clearly Currently, within the UK, control of hospital-acquired variation in medical practice with regard to licensing, avail- infection by C difficile, MRSA and pathogens with extended ability, choice, dose, route of administration and duration of b-lactamase activity is a priority of local and strategic health therapy, which is more a reflection of local custom and practice authorities. In line with the principles of prudent use of than robust scientific evidence. The literature review for the antibiotics, the current guidelines have been modified to discourage period 1981–2008 provided only 19 acceptable articles relevant unnecessary use of broad-spectrum antibiotics, especially cephalospor- 277 364–381 [Ib] [Ib] [Ib] [Ib] [II] [Ib] to the antibiotic management of CAP. ins and fluoroquinolones. The development of refined techniques http://thorax.bmj.com/ [Ib] [Ib] [Ib] [Ib] [Ib] [Ib] [Ib] [Ib] [Ib] [Ib] [Ib] [Ib] [Ib] The remainder were for severity stratification (see Section 6) have enabled a strategy rejected for the following reasons: inadequately powered studies of targeted antibiotic escalation, which should restrict the use of or a retrospective design,102 382–400 non-blinded/non-randomised empirical potent broad-spectrum therapy to those cases in studies,274 401–405 antibiotic not available in the UK or with- which it is necessary. drawn,357 361 406–441 study population or management unrepresen- As stated elsewhere, ‘‘it is important to recognise that these tative of normal clinical practice in the UK,377 442–450 or they are simply guidelines and reflect our interpretation of good included mixed lower respiratory tract infections including practice within an evolving area. Guidelines cannot capture 377 419 451 452 CAP. every clinical situation and it therefore remains the responsi- on October 1, 2021 by guest. Protected copyright. Among the studies reviewed, few were conducted within a bility of the physician to balance the history and clinical healthcare system comparable to that of the UK. Others were features, assess the importance of risk factors and interpret local designed to support the licensing of new therapies. For this epidemiology and laboratory data in order to make the best reason, they are primarily designed to demonstrate equivalence judgement for an individual patient’’.453 [IVa] between the new agent and comparator therapy which may or may not have been selected in accordance with current standard (A) EMPIRICAL THERAPY management. This invariably makes it difficult to offer evidence-based recommendations since superiority of a parti- 8.7 Empirical antibiotic choice for CAP treated in the community cular regimen is rarely identified. Likewise, matters of differ- Most patients with pneumonia are treated successfully in the ential safety for the various regimens is difficult to assess since community in the absence of any microbial definition of an this information is essentially a by-product of these licensing infecting micro-organism(s). The decision to manage a patient studies, is rarely standardised and has often not been compared in the community is based on a range of factors which include with current standard therapy. an assessment that the pneumonia is of low severity, that oral therapy is appropriate and will be complied with, and that the 8.6 Formulations of these recommendations social circumstances and available care for an individual are The recommendations for treatment have been made on the satisfactory. basis of assessing a matrix of laboratory, clinical, pharmacoki- Empirical therapy is primarily directed at S pneumoniae which netic and safety data, interpreted in an informed manner. While remains the leading cause of CAP (see Section 3).243 [Ia] Apart this remains an unsatisfactory basis for making robust evidence- from M pneumoniae, atypical pathogens, Legionella spp and b- based recommendations, it highlights the need for appropriate, lactamase producing bacteria are uncommon in the community prospective, randomised controlled studies designed to address setting. M pneumoniae exhibits epidemic periodicity every iii34 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

4–5 years largely, has a low mortality rate and affects younger c Those with features of moderate or high severity Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from persons. A policy for initial empirical therapy that aimed to infection should be admitted urgently to hospital. [C] always cover this pathogen was considered inappropriate. For these reasons, as well as the issues of current practice, 8.8 Should general practitioners administer antibiotics prior to cost, wide experience and drug tolerance, amoxicillin remains hospital transfer in those patients who need admission? the preferred agent. The alternative agents for those intolerant There is no direct evidence upon which to provide clear of amoxicillin are doxycycline and the macrolides clarithromy- guidance on this question. There is, however, some circum- 277 [Ib] cin and erythromycin. Recommendation of a tetracycline stantial evidence to suggest that early antibiotics are of benefit as an alternative therapy has been adopted on the basis of lower in high severity pneumonia. resistance rates among pneumococci (fig 9) and activity against Delay in prescribing antibiotics for patients in hospital with atypical pathogens. Reduced gastrointestinal intolerance and an diagnosed pneumonia is associated with a worse outcome464 465 easier dosing schedule are the major reasons for recommending [III] [III] and, in patients dying from CAP, the majority had not clarithromycin over erythromycin. Concern over the rising received prior antibiotics even though most had visited a general frequency of in vitro resistance (fig 9) of S pneumoniae to practitioner in the previous few days. In a national confidential macrolides (which is often linked to penicillin resistance) is enquiry into CAP deaths in young adults in England and Wales, recognised, yet published clinical evidence for clinical failure of 20 of the 27 fatal cases investigated had seen their general macrolides in the treatment of pneumococcal pneumonia practitioner for the illness and only 9 had received antibiotics.466 454 [III] 455 456 457 [IVa] [IVa] remains limited and controversial. [II] In the multicentre BTS study of CAP in 1982, none of the 458 [IVa] The macrolides clarithromycin and azithromycin and patients who died from pneumococcal pneumonia had received 459 [IVa] the fluoroquinolones have microbiological strengths in an antibiotic before admission. The authors concluded that vitro, yet in published studies to date have not been shown to some deaths may have been preventable and recommended that be more efficacious than standard therapy in treating patients an antibiotic active against S pneumoniae should be started as with low severity CAP. Several meta-analyses (including a soon as pneumonia is recognised.6 [Ib] In a study from New Cochrane review) of trials that have compared empirical Zealand, significantly fewer (p = 0.05) of those who died had antibiotic regimens with atypical pathogen coverage with received antibiotics before admission (20%) compared with regimens without atypical pathogen coverage in patients with those who survived (42%).467 [Ib] Currently, less than half of low severity pneumonia have not found any benefit of regimens adults admitted to hospital in the UK with high severity CAP with atypical pathogen coverage in terms of survival or clinical have already received antibiotics from their general practi- 460–462 efficacy. tioner.42 103 [III] [III] Many deaths and requirements for assisted The association of H influenzae and, to a much lesser extent, ventilation occur in the first few days of admission for high 463 M catarrhalis with acute exacerbations of COPD is recognised. severity CAP.6 37 241 [Ib] [Ib] [Ib] All of these studies provide further [II] However, both remain uncommon causes of CAP. When CAP support to the suggestion that, in cases of diagnosed pneumo- does arise with these pathogens, an even smaller percentage of nia, antibiotics should be given as early as possible, if necessary such patients will be infected with b-lactamase producing

before hospital admission. http://thorax.bmj.com/ strains. To illustrate the clinical significance of such resistance Delays do occur between general practitioner assessment in for managing CAP, it could be estimated that 5% of CAP cases the community, arranging admission, confirmation of the may be caused by H influenzae, of which 15% may be b- diagnosis in hospital and the start of treatment. Probably these lactamase producing strains in the UK. Therefore, of 500 are inevitable and will be exacerbated by transport distances and patients with CAP, only 4 may be infected with such antibiotic- ambulance availability and prioritisation, bed availability and resistant strains. triage in the medical assessment unit or emergency department. A view that specific pathogens are associated with other Delays between admission and receiving antibiotics of .6h comorbid diseases (eg, H influenzae and COPD) to increase the have been reported for younger adults dying in hospital of CAP on October 1, 2021 by guest. Protected copyright. risk of CAP is not supported by the literature. For these reasons, (average delay 260 min),284 [III] although this study was these guidelines do not offer alternative regimens for patients conducted before medical assessment units were introduced with or without comorbid illness, while recognising that such into most UK hospitals. diseases can affect the severity of CAP in an individual. From time to time, general practitioners do see patients who The current concern over the increasing prevalence of are severely ill with what appears to be pneumonia. In such pneumococci with reduced susceptibility to penicillin is circumstances, treatment should commence as soon as possible, recognised. However, the incidence of highly resistant strains providing it does not delay transfer to hospital. When general (MIC >4 mg/l) remains uncommon in the UK. Furthermore, practitioners feel treatment in such circumstances is needed, it the rarity of documented clinical failures among penicillin- should aim to cover pneumococcal pneumonia—the common- resistant pneumococcal pneumonia, if treated with adequate est cause of high severity CAP—with intravenous penicillin G doses of penicillin, is the basis for endorsing oral amoxicillin as 1.2 g or oral amoxicillin 1 g orally (or clarithromycin 500 mg in first-line therapy at a dosage of 500 mg three times daily. patients with penicillin sensitivity). General practitioners are likely to carry such antibiotics with them as parenteral penicillin is recommended as the immediate treatment for Recommendations suspected meningococcal infection. Ambulance services should c For patients treated in the community, amoxicillin allocate to patients with pneumonia a high priority for transfer remains the preferred agent at a dose of 500 mg three to hospital. times daily. [A+] Prescribing antibiotics does have an influence on some c Either doxycycline [D] or clarithromycin [A2] are microbiological investigations.6 [Ib] However, when general appropriate as an alternative choice, and for those practitioners feel a patient is severely ill or circumstances suggest patients who are hypersensitive to penicillins. that delays in transfer will slow assessment and treatment in

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii35 BTS guidelines

hospital, concern over the potential effect on subsequent 28.3%) in the number of patients diagnosed with ‘‘CAP’’ who Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from investigations is not a reason to withhold treatment. actually had a normal chest radiograph470 and an increase in Inappropriate antibiotic use is a major concern both in inappropriate antibiotic use.471 [III] community and hospital settings. The clinical likelihood of CAP We have sought to offer recommendations that encourage therefore needs to be taken into account when considering prompt and appropriate antibiotic treatment of patients with antibiotic treatment at the time of hospital referral. It is CAP but that avoid forcing clinicians to diagnose and treat important to state that, as with the whole of this document, pneumonia when there is genuine uncertainty. The pivotal role these guidelines refer to patients with CAP and not to the much of the chest radiograph in confirming or refuting a diagnosis of larger group of patients with non-pneumonic lower respiratory CAP in patients admitted with suspected CAP is emphasised in tract infection or exacerbations of COPD. Section 5.2. It is also recognised that, in a minority of patients, atypical presentations of CAP may result in a delay in diagnosis. Summary c Delays occur in the process of admitting patients to hospital Recommendations with CAP and them receiving antibiotics. [III] c A diagnosis of CAP should be confirmed by chest c There is direct and indirect evidence that administering radiography before the commencement of antibiotics antibiotics early is important in the outcome of CAP, in the majority of patients. Selected patients with life- particularly when the patient is assessed as being severely ill. threatening disease should be treated based on a [Ib] presumptive clinical diagnosis of CAP. In such c Less than half of patients admitted with high severity CAP instances, an immediate chest radiograph to confirm have received antibiotics before admission, even though they the diagnosis or to indicate an alternative diagnosis is may have seen their general practitioner. [III] indicated. [D] c Most deaths from CAP occur shortly after admission. [Ib] c All patients should receive antibiotics as soon as the diagnosis of CAP is confirmed. D] This should be c Pre-admission antibiotics can negatively influence the results of subsequent microbiological investigations, [Ib] before they leave the initial assessment area (emer- but this is not seen as a reason for withholding antibiotics if gency department or medical assessment unit). The the general practitioner feels they are indicated. objective for any service should be to confirm a diagnosis of pneumonia with chest radiography and initiate antibiotic therapy for the majority of patients Recommendations with CAP within 4 h of presentation to hospital. [B2] c For those patients referred to hospital with suspected CAP and where the illness is considered to be life- threatening, general practitioners should administer 8.10 Empirical antibiotic choice for adults hospitalised with low antibiotics in the community. [D] Penicillin G 1.2 g severity CAP Approximately 20% of patients with CAP are hospitalised in the intravenously or amoxicillin 1 g orally are the pre- http://thorax.bmj.com/ ferred agents. UK (see Section 2). The reasons for hospitalisation vary and c For those patients referred to hospital with suspected include severity of the infection, an unsatisfactory response to high severity CAP and where there are likely to be treatment initiated by the general practitioner, significant delays of over 6 h in the patient being admitted and comorbid illness and non-clinical reasons such as inappropriate treated in hospital, general practitioners should con- home circumstances suitable for community management. sider administering antibiotics in the community. [D] It is recognised that a significant number of patients with low severity pneumonia who might otherwise be adequately

8.9 When should the first dose of antibiotic be given to patients managed in the community are admitted to hospital for non- on October 1, 2021 by guest. Protected copyright. admitted to hospital with CAP? clinical reasons (advanced age, personal or family preference, The prompt administration of antibiotics to patients with inadequate home care or adverse social circumstances). Others proven CAP is good practice, matches patient expectation and is will be admitted who have not received antibiotic therapy. They supported by some data demonstrating improved clinical cannot be considered to have failed community treatment and, outcomes. One large retrospective study of patients aged as such, initial therapy with a single agent is considered 65 years and older admitted with CAP demonstrated a 15% appropriate (see table 5). Furthermore, M pneumoniae is an reduction in 30-day mortality for patients treated within 8 h.464 important contributor to the overall incidence of atypical [III] A further retrospective study in patients aged 65 years and pathogens but is an infrequent cause of CAP in elderly patients. older admitted with CAP and who had not received antibiotics This provides a further justification for simple monotherapy in before admission reported similar results.468 [III] the hospitalised elderly patient with low severity CAP. In all However, the diagnosis of CAP is not always evident on such circumstances, patient management requires careful admission to hospital. One study reported that 22% of patients clinical judgement and regular reviews. with CAP had atypical presentations which led initially to Following initial assessment and empirical therapy, progress diagnostic uncertainty.469 Concerns have therefore been raised should be monitored carefully. The route and choice of that undue emphasis on early antibiotic administration will lead antibiotic treatment will require adjustment, either by stepping to an increase in inaccurate diagnoses and consequently an up and broadening the spectrum of microbiological activity in increase in inappropriate antibiotic use. Studies from the USA the light of clinical deterioration or as a result of positive have shown that, following a recommendation that the time to microbiological information, or stepping down with improve- first antibiotic dose should be less than 4 h for all patients with ment as discussed below. The review of antibiotic therapy CAP, there was a 39% reduction in the accuracy of emergency forms an obvious and essential part of the regular clinical review department diagnosis of CAP, an increase (from 20.6% to of patients with CAP. iii36 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

Recommendations benefit of this strategy against the risk of undertreating Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from c Most patients with low severity CAP can be ade- pneumococcal pneumonia (erythromycin resistance of about quately treated with oral antibiotics. [C] 9%; see Section 8.3 and fig 9). c Oral therapy with amoxicillin is preferred for patients with low severity CAP who require hospital admission Recommendations for other reasons such as unstable comorbid illnesses c Most patients with moderate severity CAP can be or social needs. [D] adequately treated with oral antibiotics. [C] c When oral therapy is contraindicated, recommended c Oral therapy with amoxicillin and a macrolide is parenteral choices include intravenous amoxicillin or preferred for patients with moderate severity CAP benzylpenicillin, or clarithromycin. [D] who require hospital admission. [D] – Monotherapy with a macrolide may be suitable for 8.11 Empirical antibiotic choice for adults hospitalised with patients who have failed to respond to an adequate moderate severity CAP course of amoxicillin prior to admission. Deciding on The principles of antibiotic selection for moderate severity CAP the adequacy of prior therapy is difficult and is a managed in hospital are similar to those for its management in matter of individual clinical judgement. It is there- the community. The current guidelines incorporate a stratified fore recommended that combination antibiotic ther- approach based on disease severity (see Section 6). The apy is the preferred choice in this situation and that predominant pathogen will be S pneumoniae. However, overall the decision to adopt monotherapy is reviewed on atypical pathogens including Legionella spp account for approxi- the ‘‘post take’’ round within the first 24 h of mately 20% of defined infections. Therefore, in patients who are admission. [D] admitted with moderate severity disease, oral therapy with a c When oral therapy is contraindicated, the preferred combined b-lactam/macrolide regimen is recommended. parenteral choices include intravenous amoxicillin or When oral therapy is inappropriate, parenteral amoxicillin or benzylpenicillin, together with clarithromycin. [D] penicillin G are offered as alternatives to oral amoxicillin, with c For those intolerant of penicillins or macrolides, oral clarithromycin given twice a day as the preferred macrolide for doxycyline is the main alternative agent. Oral levo- parenteral therapy. floxacin and oral moxifloxacin are other alternative For patients intolerant of penicillin and in whom oral therapy choices. [D] is inappropriate, intravenous levofloxacin once daily or a c When oral therapy is contraindicated in those intoler- combination of intravenous cephalosporin with intravenous ant of penicillins, recommended parenteral choices clarithromycin are appropriate alternative choices. Institutions include levofloxacin monotherapy or a second-genera- wishing to avoid the use of quinolones and cephalosporins in tion (eg, cefuroxime) or third-generation (eg, cefotax- these patients may wish to consider monotherapy with ime or ceftriaxone) cephalosporin together with intravenous clarithromycin, but must weigh the ecological clarithromycin. [D] http://thorax.bmj.com/

Table 5 Initial empirical treatment regimens for community acquired pneumonia (CAP) in adults Pneumonia severity (based on clinical judgement supported by CURB65 severity score) Treatment site Preferred treatment Alternative treatment

Low severity Home Amoxicillin 500 mg tds orally Doxycycline 200 mg loading dose then 100 mg (eg, CURB65 = 0–1 or CRB65 score orally or clarithromycin 500 mg bd orally =0,,3% mortality) on October 1, 2021 by guest. Protected copyright.

Low severity Hospital Amoxicillin 500 mg tds orally Doxycycline 200 mg loading dose then 100 mg (eg, CURB65 = 0–1,,3% mortality) If oral administration not possible: amoxicillin 500 mg tds IV od orally or clarithromycin 500 mg bd orally but admission indicated for reasons other than pneumonia severity (eg, social reasons/unstable comorbid illness)

Moderate severity Hospital Amoxicillin 500 mg –1.0 g tds orally plus clarithromycin 500 mg Doxycycine 200 mg loading dose then 100 mg (eg, CURB65 = 2, 9% mortality) bd orally orally or levofloxacin 500 mg od orally or If oral administration not possible: amoxicillin 500 mg tds IV or moxifloxacin 400 mg od orally* benzylpenicillin 1.2 g qds IV plus clarithromycin 500 mg bd IV

High severity Hospital (consider Antibiotics given as soon as possible Benzylpenicillin 1.2 g qds IV plus either (eg, CURB65 = 3–5, 15–40% critical care review) Co-amoxiclav 1.2 g tds IV plus clarithromycin 500 mg bd IV levofloxacin 500 mg bd IV or ciprofloxacin mortality) (If legionella strongly suspected, consider adding levofloxacin{) 400 mg bd IV OR Cefuroxime 1.5 g tds IV or cefotaxime 1 g tds IV or ceftriaxone 2 g od IV, plus clarithromycin 500 mg bd IV (If legionella strongly suspected, consider adding levofloxacin{) bd, twice daily; IV, intravenous; od, once daily; qds, four times daily; tds, three times daily. *Following reports of an increased risk of adverse hepatic reactions associated with oral moxifloxacin, in October 2008 the European Medicines Agency (EMEA) recommended that moxifloxacin ‘‘should be used only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of this infection’’. {Caution – risk of QT prolongation with macrolide-quinolone combination.

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii37 BTS guidelines

8.12 Empirical antibiotic choice for adults hospitalised with high Recommendations Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from severity CAP c Patients with high severity pneumonia should be Mortality is greatly increased in those with high severity treated immediately after diagnosis with parenteral pneumonia (see Section 6). The illness may progress before antibiotics. [B2] microbiological information is available. c An intravenous combination of a broad-spectrum b- Preferred and alternative initial treatment regimens are lactamase stable antibiotic such as co-amoxiclav summarised in table 5 and mostly include combination therapy together with a macrolide such as clarithromycin is with broad-spectrum b-lactams and a macrolide. While S preferred. [C] pneumoniae remains the predominant pathogen, S aureus and c In patients allergic to penicillin, a second-generation Gram-negative enteric bacilli—although uncommon—carry a (eg, cefuroxime) or third-generation (eg, cefotaxime or high mortality,243 [Ia] hence the recommendation for broad- ceftriaxone) cephalosporin can be used instead of co- spectrum b-lactam regimens in those with high severity CAP. amoxiclav, together with clarithromycin. [C] Patients hospitalised with CAP caused by Legionella spp are 219 [Ia] more likely to have high severity pneumonia. For these 8.13 When should the intravenous or the oral route be chosen? reasons, the initial empirical antibiotic regimen should also Parenteral administration of antibiotics is widely and often 472 always capture this pathogen within its spectrum of activity. unnecessarily used in managing hospitalised patients including Specific antibiotic recommendations for treating confirmed those with CAP.369 475 [Ib] [IVa] Approximately 30–50% of patients legionella infection are provided in Section 8.20. The near admitted to hospital will initially require treatment with universal availability of L pneumophila urine antigen testing parenteral antibiotics.369 [Ib] Apart from the discomfort to the means that a rapid diagnosis of L pneumophila serogroup 1 patient of inserting intravenous devices, there are significant infection can often be made early in the course of the admission. complications, notably infection. In addition, the total cost of However, the urine antigen test may be negative on admission parenteral regimens greatly exceeds orally administered therapy. and is also insufficiently sensitive to exclude Legionnaires’ Factors determining the route of administration are sum- disease, so empirical therapy for Legionnaires’ disease should not marised in box 3. Parenteral antibiotics are clearly indicated for be discontinued based solely on a negative antigen test. patients unable to swallow, where there is concern about Parenteral administration of antibiotic is recommended in adequate absorption of drug from the gut and in the presence of those with high severity CAP regardless of the patient’s ability severe pneumonia. However, many antibiotics are well absorbed or otherwise to take oral medication. This is to ensure prompt following oral administration and achieve their maximum high blood and lung concentrations of antibiotic. plasma concentration within 1–2 h. The preferred regimen includes co-amoxiclav. This agent has excellent activity against the pneumococcus, H influenzae and S Recommendations aureus, as well as activity against anaerobes. In the current guidelines, cephalosporins and fluoroquinolones are included as c The oral route is recommended in those with low and alternative but not preferred choices, largely on the basis that moderate severity CAP admitted to hospital provided + their use has been consistently associated with hospital acquired there are no contraindications to oral therapy. [B ] http://thorax.bmj.com/ infections, notably C difficile associated disease. While co- amoxiclav has also been shown to be associated with C difficile 8.14 When should the intravenous route be changed to oral? infection, the Committee considers co-amoxiclav to be less As stated above, parenteral antibiotic therapy is widely and likely to encourage C difficile overgrowth compared with often unnecessarily used among hospitalised patients with low cephalosporins and fluoroquinolones. Furthermore, use of co- and moderate severity pneumonia. This in part reflects custom amoxiclav enables transition from intravenous to oral therapy and practice but, in addition, may be driven by too liberal an without switching class of agent, a property which might help interpretation of the ‘‘criteria’’ for identifying high severity CAP physicians switch early to oral therapy which will also help for which parenteral agents are recommended. The current on October 1, 2021 by guest. Protected copyright. limit C difficile infection. practice of medicine in emergency medical admissions may also Efficacy data from prospective controlled clinical trials is not be a factor in the choice of parenteral administration where it available. However, a retrospective study suggests a reduction in provides greater confidence to admitting junior medical staff mortality for those treated with a third-generation cephalo- that the patient is receiving the ‘‘best’’ management. Oral sporin plus a macrolide,473 [III] although no additional benefit has therapy was clearly more widely adopted in the past.475 been noted in another study.474 [II] However, published evidence indicating comparable efficacy of Levofloxacin is the only licensed and available intravenous parenteral and oral regimens is limited, but has been shown for fluoroquinolone in the UK at the time of writing. It is marketed intravenous cefuroxime and oral levofloxacin.371 [Ib] in parenteral and oral formulations; since the latter is 98% The choice and timing of any change to oral therapy will be bioavailable, this indicates that it can be used in high severity affected by several factors. These include the absence of any pneumonia provided there are no contraindications to oral contraindications to oral administration, the availability of any administration. While it has modest activity against pneumo- microbiological information regarding aetiology of the infection cocci in vitro, the published evidence for efficacy in high severity and clear evidence that the patient is responding to initial CAP is reassuring.198 244 267 329 330 [Ib] [Ib] [Ib] [Ib] [Ib] However, until therapy. more clinical experience is available, we recommend combining There can be no rigid recommendation concerning the timing it with another agent active against S pneumoniae such as of transfer to oral therapy and further studies of this area are parenteral benzylpenicillin when managing high severity CAP. needed.438 476 477 [II] [Ia] [II] Any decision must be individualised on A small minority of patients will be allergic to both penicillins the basis of assessing all factors. Nonetheless, the recommended and cephalosporins. Antibiotic selection is more difficult in guideline is that oral therapy be considered in a patient who has these patients and should be discussed with the local respiratory shown clear evidence of improvement and whose temperature and microbiology services. has resolved for a period of 24 h. The features indicating iii38 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

response to parenteral therapy are summarised in box 4. This not supported by robust evidence. One RCT of adults with low Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from policy will allow a significant proportion of patients with to moderate severity pneumonia treated with amoxicillin pneumonia to be safely transferred to an oral regimen after a reported similar efficacy with a 3-day intravenous course as period of initial parenteral therapy.279 372 393 438 476 478 [II] [Ib] [Ia] [II] [Ia] [IVa] with an 8-day (3 days intravenous followed by 5 days oral) course.479 The Summary of Product Characteristics (formerly the Recommendations Drug Data Sheets) for many agents used in the treatment of CAP mention a range of treatment durations which sometimes c Patients treated initially with parenteral antibiotics differ internationally. Intracellular pathogens responsible for should be transferred to an oral regimen as soon as clinical improvement occurs and the temperature has pneumonia sometimes respond slowly, and hence a 2-week been normal for 24 h, providing there is no contra- treatment regimen has been proposed for atypical pathogens. indication to the oral route. Pointers to clinical The aim of antibiotic therapy is to ensure elimination of the improvement are given in box 4. [B+] target pathogen in the shortest time. In uncomplicated c The choice of route of administration should be infections this is likely to occur rapidly (within 3 days) with reviewed initially on the ‘‘post take’’ round and then many common respiratory pathogens such as S pneumoniae. The daily. [D] resolution of pneumonia involves not only the elimination of c Ward pharmacists could play an important role in the invading pathogen and its products, but also the subsidence facilitating this review by highlighting prescription of the host inflammatory response which together are charts where parenteral antibiotic therapy continues. responsible for the many clinical and radiographic features of [D] pneumonia. Until we have more precise methods to reliably identify microbiological and clinical end-points, the duration of therapy 8.15 Which oral antibiotics are recommended on completion of will remain subject to clinical judgement. For these reasons, the intravenous therapy? duration of therapy will vary by individual patient, disease The selection of agents for oral administration following initial severity and speed of resolution. intravenous therapy is based on antimicrobial spectrum, efficacy, safety and cost considerations. Although it may appear logical to select the oral formulation of a parenteral agent, this is Recommendations not essential and such oral agents may not meet the criteria for c For community managed and for most patients selection. For macrolides, oral clarithromycin is better tolerated admitted to hospital with low or moderate severity than oral erythromycin.364 365 [Ib] [Ib] A clinical judgement can be and uncomplicated pneumonia, 7 days of appropriate made whether to change to oral monotherapy in those who antibiotics is recommended. [C] have responded favourably to parenteral combination therapy c For those with high severity microbiologically-unde- or where there is microbiological documentation of the nature fined pneumonia, 7–10 days treatment is proposed. of the infection, in which case the recommendations in table 6 This may need to be extended to 14 or 21 days should be adopted. according to clinical judgement; for example, where S http://thorax.bmj.com/ aureus or Gram-negative enteric bacilli pneumonia is Recommendations suspected or confirmed. [C] c The antibiotic choices for the switch from intravenous to oral are straightforward where there are effective 8.17 Failure of initial empirical therapy and equivalent oral and parenteral formulations. [C] In those patients who fail to respond to initial empirical c In the case of parenteral cephalosporins, the oral therapy, several possibilities need to be considered, the first of switch to co-amoxiclav 625 mg three times daily is which is whether the correct diagnosis has been made. Clinical

recommended rather than to oral cephalosporins. [D] and radiographic review is recommended for patients managed on October 1, 2021 by guest. Protected copyright. c For those treated with benzylpenicillin + levofloxacin, in the community and in hospital to look for secondary oral levofloxacin with or without oral amoxicillin diagnoses or complications of CAP such as pleural effusion/ 500 mg–1.0 g three times daily is recommended. [D] empyema, lung abscess or worsening pneumonic shadowing. This aspect is considered in detail in Section 9. 8.16 How long should antibiotics be given for? The initial empirical antibiotic regimen may need to be The precise duration of antibiotic therapy for the management reassessed. However, compliance with and adequate absorption of microbiologically documented and non-documented CAP is of an oral regimen should first be considered. Microbiological data should be reviewed and further speci- mens examined with a view to excluding less common Box 3 Indications for parenteral and oral antibiotic therapy pathogens such as S aureus, atypical pathogens, Legionella spp, of adult CAP viruses and Mycobacteria spp. It should also be noted that mixed infections can arise in approximately 10% of patients hospita- Parenteral therapy lised with CAP. In the absence of any microbiological indicators c High severity pneumonia of infection, the management of those failing initial empirical c Impaired consciousness therapy will vary according to the severity of illness at c Loss of swallowing reflex reassessment. In patients with low severity pneumonia mana- c Functional or anatomical reasons for malabsorption ged in the community, a macrolide could be substituted for Oral therapy amoxicillin. However, when the patient’s condition has c Community managed deteriorated, admission to hospital should be considered. c Hospital managed, non-severe with no other contraindications In the patient with low or moderate severity pneumonia managed in hospital, the addition of a macrolide is recommended

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii39 BTS guidelines

Recommendations Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from Box 4 Features indicating response to initial empirical c parenteral therapy permitting consideration of oral When a change in empirical antibiotic therapy is considered necessary, a macrolide could be substituted antibiotic substitution for or added to the treatment for those with low severity pneumonia treated with amoxicillin mono- c Resolution of fever for .24 h therapy in the community or in hospital. [D] c Pulse rate ,100 beats/min c For those with moderate severity pneumonia in c Resolution of tachypnoea hospital on combination therapy, changing to doxycy- c Clinically hydrated and taking oral fluids cline or a fluoroquinolone with effective pneumococcal c Resolution of hypotension cover are alternative options. [D] c Absence of hypoxia c Adding a fluoroquinolone is an option for those with c Improving white cell count high severity pneumonia not responding to a b-lactam/ c Non-bacteraemic infection macrolide combination antibiotic regimen. [D] c No microbiological evidence of legionella, staphylococcal or Gram-negative enteric bacilli infection 8.18 Antibiotic stewardship and avoiding inappropriate antibiotic c No concerns over gastrointestinal absorption prescribing for CAP Inappropriate antibiotic prescribing is a driver for antibiotic resistance and increases the likelihood of development of C difficile infection. Given the frequency of admissions to hospital in those patients initially managed with amoxicillin alone. for suspected CAP and the difficulty in identifying a causative Changing to doxycyline or a new fluoroquinolone such as pathogen often leading to initial empirical broad-spectrum levofloxacin are alternatives. antibiotic therapy, it is timely to offer guidance to limit In the patient with high severity pneumonia already receiving inappropriate prescribing in the context of the management of a b-lactam/clarithromycin regimen, the addition of levofloxacin patients with CAP. should be considered. In addition, urgent referral to a respiratory Ensuring an accurate diagnosis of CAP is the most important physician should be made for clinical assessment including the issue in relation to the avoidance of inappropriate antibiotic possible need for bronchoscopic sampling. prescribing. One study reported that 29% of hospitalised

Table 6 Recommended treatment of microbiologically documented pneumonia and aspiration pneumonia (local specialist advice should also be sought*) Pathogen Preferred Alternative

S pneumoniae Amoxicillin 500 mg –1.0 g{ tds orally or Clarithromycin 500 mg bd orally or cefuroxine 0.75–1.5 g benzylpenicillin 1.2 g qds IV tds IV or cefotaxime 1–2 g tds IV or ceftriaxone 2 g od IV http://thorax.bmj.com/

M pneumoniae Clarithromycin 500 mg bd orally or IV Doxycycline 200 mg loading dose then 100 mg od orally C pneumoniae or fluoroquinolone{ orally or IV C psittaci Doxycycline 200 mg loading dose then 100 mg od Clarithromycin 500 mg bd orally or 500 mg bd IV C burnetii orally Legionella spp Fluoroquinolone orally or IV{1 Clarithromycin 500 mg bd orally or IV (or, if necessary, azithromycin in countries where this antibiotic is used for managing pneumonia) on October 1, 2021 by guest. Protected copyright. H influenzae Non-b-lactamase-producing: amoxicillin 500 mg tds Cefuroxime 750 mg –1.5 g tds IV or cefotaxime 1–2 g tds orally or IV IV or ceftriaxone 2 g od IV or fluoroquinolone{ orally or IV b-lactamase-producing: co-amoxiclav 625 mg tds orally or 1.2 g tds IV Gram-negative Cefuroxime 1.5 g tds or cefotaxime 1–2 g tds IV or Fluoroquinolone{ IV or imipenem 500 mg qds IV or enteric bacilli ceftriaxone 1–2 g bd IV meropenem 0.5–1.0 g tds IV

P aeruginosa Ceftazidime 2 g tds IV plus gentamicin or tobramycin Ciprofloxacin 400 mg bd IV or piperacillin 4 g tds IV, plus (dose monitoring) gentamicin or tobramycin (dose monitoring)

S aureus Non-MRSA: flucloxacillin 1–2 g qds IV ¡ rifampicin MRSA: vancomycin 1 g bd IV (dose monitoring) or 600 mg od or bd orally/IV linezolid 600 mg bd IV or teicoplanin 400 mg bd IV ¡ rifampicin 600 mg od or bd orally/IV

Aspiration Co-amoxiclav 1.2 g tds IV Seek local microbiology advice pneumonia bd, twice daily; IV, intravenous; od, once daily; tds, three times daily. *Treatment can be modified once the results of sensitivity testing are available. {A higher dose of 1.0 g tds is recommended for infections documented to be caused by less susceptible strains (minimum inhibitory concentration .1.0 mg/l). {Currently UK licensed and available suitable fluoroquinolones include ciprofloxacin, ofloxacin and levofloxacin. Moxifloxacin can be used for patients who cannot be treated or have failed treatment with other antibacterials. 1Specifically for legionella pneumonia, the large majority of published experience regarding the efficacy of fluoroquinolones is only with levofloxacin. For high severity or life-threatening legionella pneumonia, combination therapy including the preferred and an alternative antibiotic can be considered for the first few days (see text for further details). Rifampicin is not recommended on its own but could be considered as the second additional antibiotic. iii40 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

patients treated for CAP did not have radiographic abnormal- methicillin-sensitive, although the recent increase in MRSA in Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from ities.471 [III] hospitalised patients may result in subsequent readmission with In patients with CAP, broad-spectrum intravenous antibiotics an MRSA infection which may include CAP. Options for should only be used following careful consideration, taking into methicillin-sensitive and methicillin-resistant infections are account severity of illness, likely pathogens involved and based on parenteral administration in view of the serious patient-specific factors such as the ability to tolerate oral nature of staphylococcal pneumonia. medication. Whenever appropriate, narrow-spectrum oral anti- biotics should be used preferentially. Recommendations c If a specific pathogen has been identified, the anti- Recommendations biotic recommendations are summarised in table 6 [C]. c The diagnosis of CAP and the decision to start antibiotics should be reviewed by a senior clinician at the earliest opportunity. There should be no barrier 8.20 Specific issues regarding the management of Legionnaires’ to discontinuing antibiotics if they are not indicated. disease [D] Legionella infection is unique as a cause of CAP owing to the c The indication for antibiotics should be clearly docu- mode of spread and the importance of trying to identify the mented in the medical notes. [D] source to prevent further cases. The infection is acquired by c The need for intravenous antibiotics should be inhaling water mist containing legionella bacteria, which are reviewed daily. [D] commonly found in natural and manmade water systems. c De-escalation of therapy, including the switch from Common sources include drift from evaporative cooling towers intravenous to oral antibiotics, should be considered as and aerosols generated from showers, aerated hot tubs, soon as is appropriate, taking into account response to humidifiers and potable water. In addition, the propensity to treatment and changing illness severity. [D] cause severe illness including multiple organ failure and the lack c Strong consideration should be given to narrowing the of response to b-lactam antibiotics suggests that specific spectrum of antibiotic therapy when specific patho- guidance will be helpful to clinicians managing a case. gens are identified or when the patient’s condition Detection of legionella urinary antigen using a rapid improves. [D] technique has revolutionised the early diagnosis of pneumonia c Where appropriate, stop dates should be specified for caused by L pneumophila serogroup 1 which is responsible for antibiotic prescriptions. [D] over 90% of community cases in the UK and Europe. This is a highly sensitive and specific test, particularly in patients who (B) SPECIFIC PATHOGEN-DIRECTED ANTIBIOTIC are unwell enough or who have been ill long enough to require THERAPY hospital admission (see Section 6). Although urinary antigen detection is now the most valuable and frequently used

diagnostic test, sputum culture still has a vital role in diagnosing http://thorax.bmj.com/ 8.19 What are the optimum antibiotic choices when specific infection caused by other legionella serogroups and species. It is pathogens have been identified? also invaluable for matching legionella species and strains In routine clinical practice, only about one-third to one-quarter identified from cases, with those positive water cultures from of patients with CAP admitted to hospital will be defined a potential source. This can help prevent further cases of microbiologically. Of these, some such as mycoplasma, chla- infection. It is therefore important to send off sputum or mydophila and C burnetii infection will be diagnosed late in the respiratory secretions specifically for legionella culture, even in illness on the basis of seroconversion, reducing the opportunity proven cases and after appropriate antibiotics have started (see for early targeted therapy. Among patients managed in the Section 5.11.5). on October 1, 2021 by guest. Protected copyright. community, very few will be microbiologically defined. Legionnaires’ disease is not currently a notifiable disease in When a pathogen has been identified, specific therapy as the UK, but urgent action to investigate the source of infection summarised in table 6 is proposed. In transferring patients from is essential. In proven cases of legionella pneumonia, the empirical to pathogen-targeted therapy, the regimen and route clinician should liaise with the clinical microbiologist to confirm of administration will be determined by the continued need for that the local Health Protection Unit has been informed. The parenteral therapy and known drug intolerance. Hence, table 6 Health Protection Unit should initiate immediate investigations provides preferred and alternative regimens for intravenous or and this will include recording details of recent travel and oral administration. However, it should be remembered that activities within the 2 weeks before illness onset (the usual approximately 10% (see Section 3) of infections will be of mixed incubation period is 2–10 days) from the patient or their aetiology, although many such co-pathogens will be viral and relatives to assist epidemiological investigation. Clinicians hence not influenced by antibiotic choice. These recommenda- should help by explaining the need for this to patients and tions are again based on a synthesis of information which relatives; this is important, especially at a time when the patient includes in vitro activity of the drugs, appropriate pharmaco- may be very unwell and their relatives distressed. The Health kinetics and clinical evidence of efficacy gleaned from a variety Protection Agency (HPA) will also request a clinical information of studies. The choice of agent may be modified following the sheet to be completed which provides very valuable (anon- availability of sensitivity testing or following consultation with ymous) clinical and outcome data to update the ongoing a specialist in microbiology, infectious disease or respiratory national and European data sets which are available from the medicine. HPA website (www.hpa.org.uk) or, for Scotland, from Health Currently, S pneumoniae highly resistant to penicillin (MIC Protection Scotland (www.hps.scot.nhs.uk) and the European >4 mg/l) is uncommon in the UK. S aureus is an uncommon Working Group for Legionella Infections (www.ewgli.org). cause of CAP in the UK. Most community isolates are Further details about the investigation of a potential source of

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii41 BTS guidelines

legionella infection and the management of sporadic cases can It has become accepted dogma that prolonged antibiotic Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from be found at the HPA website (www.hpa.org.uk) under the therapy of 2–3 weeks is needed for legionella pneumonia to section Infectious DiseasesRInfections A-ZRLegionnaires’ prevent relapses. This is based on a few anecdotal cases reported diseaseRGuidelines. following the Philadelphia outbreak in 1976, largely involving There are no robust trials comparing the efficacy of different immunocompromised patients.487 [III] However, there is no antibiotics for treating Legionnaires’ disease, but in vitro studies evidence to support the statement that patients with commu- and clinical experience in the form of observational case series nity acquired legionella pneumonia require longer therapy than support the use of quinolones, macrolides, azithromycin and other patients with CAP, and the duration of therapy should be rifampicin, with fluoroquinolones being the most effective guided as usual by clinical judgement. agents. By contrast, antibiotics are not required for the non- pneumonic form of legionellosis—pontiac fever—which pre- Recommendations sents as a self-limiting flu-like illness with an incubation period of only 1–2 days. c As soon as a diagnosis of legionella pneumonia has A recent paper regarding the antibiotic therapy for been made, the clinician should liaise with the clinical Legionnaires’ disease480 [IVa] reviewed the combined results from microbiologist to confirm that the local Health Protection Unit has been informed. The Health three recent observational studies of 458 patients with Protection Unit is responsible for promptly investigat- Legionnaires’ disease managed with either a macrolide or a ing the potential sources of infection. [D] fluoroquinolone (mostly levofloxacin in an initial dose of c The clinician should assist, where appropriate, in the 500 mg twice daily)481–483 [II] [II] [II] and concluded that fluoroqui- gathering of clinical and epidemiological information nolones appeared to have significant advantages over macrolides from the patient and their relatives to aid the source when comparing the end points of defervescence, side effects investigation. [D] and hospital stay; however, the mortality rate was similar. c Sputum or respiratory secretions should be sent off As the evidence base regarding the clinical efficacy of specific specifically for legionella culture in proven cases, even antibiotics is weak, consensus is used to make recommenda- after appropriate antibiotics have started. [D] tions. Fluoroquinolones are regarded as the antibiotic of choice c For low and moderate severity community acquired for proven legionella infection and, in such cases, their use legionella pneumonia, an oral fluoroquinolone is should not be restricted by general ecological concerns over recommended. In the unusual case when this is not quinolone use. possible due to patient intolerance, a macrolide is an For low and moderate severity community acquired legionella alternative. [D] Antibiotics are not required for the infection, an oral fluoroquinolone is recommended and should non-pneumonic self-limiting form of legionellosis— be prescribed unless there is definite patient intolerance which pontiac fever. [D] prevents its use. In this unusual circumstance, a macrolide is an c For the management of high severity or life threaten- alternative. (azithromycin is rarely used in the UK for CAP but ing legionella pneumonia, a fluoroquinolone is recom- is an alternative in countries where it is recommended for CAP).

mended. For the first few days this can be combined http://thorax.bmj.com/ For the management of high severity or life-threatening withamacrolide(azithromycinisanoptionin legionella pneumonia, a fluoroquinolone should be used wher- countries where it is used for pneumonia) or rifampi- ever possible. There are no robust data on the use of cin as an alternative. [D] Clinicians should be alert to combination antibiotics for high severity legionella pneumonia. the potential small risk of cardiac electrophysiological However, in most circumstances, patients will already be on abnormalities with quinolone-macrolide combina- empirical combined antibiotic therapy for severe CAP which tions. includes a macrolide (clarithromycin) at the time the diagnosis c Duration of therapy should be as for microbiologically- undefined CAP (for those with low to moderate is made. Thus, with the knowledge of the significant mortality on October 1, 2021 by guest. Protected copyright. of high severity legionella pneumonia and the possibility of dual severity pneumonia, 7 days treatment is proposed; infection, continuing combined antibiotic therapy with a for those with high severity pneumonia, 7–10 days macrolide in addition to the fluoroquinolone is recommended treatment is proposed—this may need to be extended to 14 or 21 days, see Section 8.16) and should be during the crucial first few days. Azithromycin (in countries guided by clinical judgement. [D] where this antibiotic is used for pneumonia) is an alternative to clarithromycin. However, clinicians should be alert to the potential small risk of cardiac electrophysiological abnormalities 8.21 Specific issues regarding Panton-Valentine Leukocidin- including prolongation of the QT interval on the ECG with the producing Staphylococcus aureus 484 [IVa] recommended combination, particularly if other pro- Necrotising pneumonia caused by a Panton-Valentine arrhythmic risk factors are present. Rifampicin has traditionally Leukocidin (PVL)-producing strain of S aureus (PVL-SA, either also been offered as an alternative antibiotic to add as the MSSA or MRSA) is rare in the UK and Europe. If strongly second antibiotic in combined therapy and we include it as a suspected, blood cultures and respiratory samples should have recommended alternative. However, one small cohort observa- an urgent Gram stain and be cultured on non-selective media to tional study of 32 patients with legionella pneumonia reported aid recovery of pathogens. Clinicians strongly suspecting that the addition of rifampicin to clarithromycin therapy infection due to PVL-SA should liaise with their local micro- offered no additional benefit in terms of recovery and that biology laboratory to ensure sensitivity testing and toxin gene those receiving rifampicin had a longer length of stay in profiling are carried out. hospital.485 [III] With parenteral rifampicin there is also a risk of Detailed guidance on the specific management of patients hyperbilirubinaemia, which usually resolves on stopping the with necrotising pneumonia due to PVL-SA is available from the drug.486 [III] Further studies are indicated in the optimal HPA website (http://www.hpa.org.uk/web/HPAwebFile/ treatment of high severity legionella pneumonia. HPAweb_C/1218699411960). iii42 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

Recommendations The presence of bilateral pleural effusions in CAP is associated Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from 259 [II] c PVL-SA infection is a rare cause of high severity with increased mortality. Although most effusions will pneumonia and can be associated with rapid lung resolve with antibiotic therapy alone, it is recommended that cavitation and multiorgan failure. Such patients should thoracocentesis is performed promptly in patients with para- be considered for critical care admission. [D] pneumonic effusion admitted to hospital. Those patients shown c If PVL-SA necrotising pneumonia is strongly sus- to have an empyema (defined as the detection of cloudy fluid, pected or confirmed, clinicians should liaise urgently pus or organisms on Gram stain or culture492 [II])ora with the microbiology department in relation to complicated parapneumonic effusion (defined as clear pleural further antibiotic management and consider referral fluid with a pH ,7.2493 [II]) should then have early and effective to the respiratory medicine department for clinical pleural space drainage. Pleural fluid for pH should be collected management advice. [D] anaerobically in a heparinised blood gas syringe and measure- c Current recommendations for the antibiotic manage- ment is performed in a blood gas analyser. ment of strongly suspected necrotising pneumonia The incidence of empyema in patients admitted to hospital include the addition of a combination of intravenous with CAP in a Canadian study was 0.7–1.3%. The in-hospital linezolid 600 mg bd, intravenous clindamycin 1.2 g mortality in these patients was 4.2%.494 [II] Other data indicate qds and intravenous rifampicin 600 mg bd to the an increase in the incidence of patients hospitalised with initial empirical antibiotic regimen. As soon as PVL-SA empyema over the last decade.495 496 [III] [III] infection is either confirmed or excluded, antibiotic Recognition of empyema is important as delayed thoraco- therapy should be narrowed accordingly. [D] centesis and chest tube drainage lead to longer and more costly hospitalisation.491 [III] Further details on the management of SECTION 9 COMPLICATIONS AND FAILURE TO IMPROVE empyema are available in the BTS guidelines on the manage- 9.1 What factors and action should be considered in patients ment of pleural infection.497 who fail to improve in hospital? For patients in hospital with CAP, the median time to Recommendations improvement in heart rate and blood pressure is 2 days and in temperature, respiratory rate and oxygen saturation is 3 days. c Early thoracocentesis is indicated for all patients with Failure to improve with initial management may occur in 6– a parapneumonic effusion. [D] 24% of patients.488 489 [II] [II] c Those found to have an empyema or clear pleural fluid Independent risk factors for failure to improve that have been with pH ,7.2 should have early and effective pleural identified include multilobar involvement, cavitating pneumo- fluid drainage. [C] nia, presence of a pleural effusion, co-existing liver disease, c The BTS guidelines for the management of pleural cancer or neurological disease, aspiration pneumonia, legionella infection should be followed. [D] pneumonia, Gram-negative pneumonia, leucopenia, high disease severity on admission and inappropriate antimicrobial ther-

9.2.2 Lung abscess http://thorax.bmj.com/ apy.488–490 [II] [II] [II] Patients who fail to improve have a poorer prognosis. Studies Lung abscess is a rare complication of CAP, being seen most have reported a mean increase in length of hospital stay of commonly in the debilitated or alcoholic patient and following 4 days489 [II] and an increase in mortality.490 [II] aspiration. Infection with anaerobic bacteria, S aureus, Gram- Failure to improve should lead to consideration of various negative enteric bacilli or S milleri (in the presence of poor dental possibilities summarised in box 5. hygiene) should be considered. Most patients respond to appropriate antibiotics. A prolonged course of antibiotics may be required, although there is a lack of evidence on which to Recommendations base firm recommendations regarding the optimum duration of on October 1, 2021 by guest. Protected copyright. c For patients who fail to improve as expected, there antimicrobial therapy. Early surgical drainage via pneumonot- should be a careful review by an experienced clinician omy may occasionally be needed. of the clinical history, examination, prescription chart and results of all available investigation results. [D] Recommendations c Further investigations, including a repeat chest radio- graph, C-reactive protein and white cell count and c Less usual respiratory pathogens including anaerobes, further specimens for microbiological testing should S aureus, Gram-negative enteric bacilli and S milleri be considered in the light of any new information after should be considered in the presence of lung abscess. the clinical review. [D] [D] c Referral to a respiratory physician should be consid- c Prolonged antibiotic therapy of up to 6 weeks depend- ered. [D] ing on clinical response and occasionally surgical drainage should be considered. [D] 9.2 What are the common complications of CAP? A brief description of the common complications of CAP is 9.2.3 Metastatic infection given below. Complications associated with specific infections Patients with septicaemia associated with pneumonia can are summarised in table 7. occasionally develop metastatic infection. Meningitis, peritoni- tis, endocarditis and septic arthritis have all been reported. 9.2.1 Pleural effusion and empyema Purulent pericarditis can occur, usually in direct relation to an Parapneumonic effusions develop in 36–57% of bacterial empyema. pneumonias admitted to hospital and can be the cause of Most such complications can be detected by careful history persisting pyrexia despite adequate antibiotic treatment.491 [II] and examination.

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii43 BTS guidelines Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from Box 5 Reasons for failure to improve as expected Table 7 Some complications associated with specific infections Pathogen Complications Incorrect diagnosis or complicating condition S pneumoniae Septicaemia, pyopneumothorax, pericarditis/endocarditis, meningitis/brain abscess, peritonitis, arthritis, herpes c Common labialis – Pulmonary embolism/infarction M pneumoniae Meningoencephalitis, aseptic meningitis, Guillain-Barre´ – Pulmonary oedema syndrome, transverse myelitis, cerebellar ataxia, – Bronchial carcinoma ascending polyneuropathy, pericarditis, myocarditis, diarrhoea, haemolytic anaemia, skin rashes, – Bronchiectasis polyarthropathy, hepatitis, pancreatitis, splenomegaly, – Slow response in the elderly patient acute glomerulonephritis, haemorrhagic myringitis c Uncommon Legionella spp Confusion, encephalomyelitis, Guillain-Barre´syndrome, – Pulmonary eosinophilia/eosinophilic pneumonia cerebellar signs, pericarditis, hyponatraemia, renal failure, rhabdomyolysis and myositis, diarrhoea, polyarthropathy – Cryptogenic organising pneumonia Jaundice/abnormal liver function, pancreatitis, – Pulmonary alveolar haemorrhage thrombocytopenia – Foreign body C burnetii Optic neuritis, hepatitis, haemolytic anaemia, – Congenital pulmonary abnormality (eg, lobar osteomyelitis, endocarditis with chronic infection sequestration) S aureus Pneumatoceles and/or pneumothorax (especially in children), septicaemia, lung abscess, metastatic infection Unexpected pathogen or pathogens not covered by antibiotic choice disease preventable and potentially preventable through immu- c Pathogens always resistant to common antibiotics (eg, an ‘‘atypical pathogen’’ not responding to penicillin) nisation. A full review and discussion relating to the cost effectiveness of influenza and pneumococcal vaccination, c Pathogens sometimes resistant to commonly used antibiotics (eg, ampicillin-resistant H influenzae; penicillin-resistant S including the role of the newer pneumococcal conjugate pneumoniae; mycobacteria) vaccines, was deemed to be outside the remit of this document. Existing Department of Health guidelines are referred to Antibiotic ineffective or causing allergic reaction (the Green book; see http://www.dh.gov.uk/en/Publichealth/ c Poor absorption of oral antibiotic Healthprotection/Immunisation/Greenbook/DH_4097254). c Inadequate dose c Antibiotic hypersensitivity Recommendations c Patient not receiving or taking prescribed antibiotic c Department of Health guidelines in relation to influ- Impaired local or systemic defences enza and pneumococcal immunisation of at-risk indi- c Local (eg, bronchiectasis, endobronchial obstruction, viduals should be followed. [C] aspiration) c All patients aged .65 years or at risk of invasive

c Systemic immune deficiency (eg, HIV infection, pneumococcal disease who are admitted with CAP and http://thorax.bmj.com/ hypogammaglobulinaemia, myeloma) who have not previously received pneumococcal vaccine should receive 23-valent pneumococcal poly- Local or distant complications of CAP saccharide vaccine (23-PPV) at convalescence in line c Pulmonary with the Department of Health guidelines. [C] – Parapneumonic effusion – Empyema 10.2 Smoking cessation – Lung abscess Cigarette smoking, both active and passive, is a recognised

– Adult respiratory distress syndrome independent risk factor for CAP.498 499 [Ib] [Ib] Dose-response on October 1, 2021 by guest. Protected copyright. c Extrapulmonary relationships with the current number of cigarettes smoked per – Phlebitis at intravenous cannula site day, pack-years of smoking and time since quitting have been – Metastatic infection demonstrated in relation to invasive pneumococcal disease.500 [III] – Septicaemia – End organ sequelae of septicaemia (eg, renal failure) Recommendations Overwhelming infection c Smoking cessation advice should be offered to all Improvement expected too soon patients with CAP who are current smokers according c For example, in elderly patients to smoking cessation guidelines issued by the Health Education Authority.501 [B+]

SECTION 11 COMMITTEE MEMBERSHIP AND ACKNOWLEDGEMENTS SECTION 10 PREVENTION AND VACCINATION 11.1 Membership of the BTS Community Acquired Pneumonia 10.1 Influenza and pneumococcal vaccination Guidelines Committee and affiliations The prevention of CAP, particularly in those considered at high Wei Shen Lim (Chairman), Consultant Respiratory Physician, risk of infection, is an important issue in the overall manage- Nottingham University Hospitals; Simon Baudouin, Senior ment of CAP. The Joint Committee on Vaccination and Lecturer in Critical Care Medicine, Royal Victoria Infirmary Immunisation is an independent expert advisory committee and Intensive Care Society; Robert George, Director Respiratory that advises the Secretaries of State of Health, Scotland, Wales and Systemic Infections Department, Health Protection Agency and Northern Ireland on matters relating to communicable Centre for Infections, Colindale; Adam Hill, Consultant iii44 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

Respiratory Physician, Edinburgh Royal Infirmary; Conor and the contents submitted to the BTS Standards of Care Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from Jamieson, Principal Pharmacist – Anti-infectives, Heart of Committee. These are available for inspection on request from England NHS Trust and British Society of Antimicrobial the Chairman of this Committee. Chemotherapy; Ivan Le Jeune, Consultant in Acute Medicine, Competing interests: None. Nottingham University Hospitals and Society for Acute Medicine; John Macfarlane, Professor of Respiratory Medicine, Provenance and peer review: Not commissioned; not externally peer reviewed. University of Nottingham and Consultant Respiratory Physician, Nottingham University Hospitals; Robert Read, REFERENCES Professor in Infectious Diseases, University of Sheffield and 1. Macfarlane JT, Boswell T, Douglas G, et al. BTS guidelines on the management of British Infection Society; Helen Roberts, Specialist Registrar in community acquired pneumonia in adults. Thorax 2001;56(Suppl 4):1–64. 2. British Thoracic Society Pneumonia Guidelines Committee. BTS guidelines for Respiratory Medicine, Mid-Trent rotation, Nottingham the management of community acquired pneumonia in adults – 2004 update. 2004. University Hospitals; Mark Levy, General Practitioner, Royal http://www.brit-thoracic.org.uk/Portals/0/Clinical%20Information/Pneumonia/ College of General Practitioners and General Practice Airways Guidelines/MACAPrevisedApr04.pdf (accessed 15 Dec 2008). 3. Macfarlane J. Lower respiratory tract infection and pneumonia in the community. Group (GPIAG); Mushtaq Wani, Health Care of the Elderly Semin Respir Infect 1999;14:151–62. Consultant, Swansea NHS Trust and British Geriatrics Society; 4. Macfarlane J. An overview of community acquired pneumonia with lessons Mark Woodhead, Consultant Respiratory Physician, learned from the British Thoracic Society Study. Semin Respir Infect 1994;9:153–65. Manchester Royal Infirmary. 5. Marrie TJ, Durant H, Yates L. Community-acquired pneumonia requiring hospitalization: 5-year prospective study. Rev Infect Dis 1989;11:586–99. 6. British Thoracic Society. Community-acquired pneumonia in adults in British 11.2 Authorship of sections of the guidelines hospitals in 1982–1983: a survey of aetiology, mortality, prognostic factors and outcome. Q J Med 1987;62:195–220. At least two clinical experts (a lead and a partner) were 7. National Institute for Health and Clinical Excellence (NICE). National clinical identified for each of the main topic areas and were responsible guideline on management of chronic obstructive pulmonary disease in adults in for the work of critically appraising the literature and preparing primary and secondary care. Thorax 2004;51(Suppl 1):1–232. 8. British Thoracic Society Standards of Care Committee. Guidelines for the a main draft for the relevant section as described in section 1.8. management of community acquired pneumonia in childhood. Thorax 2002;57(Suppl 1). 9. Department of Health and Health Protection Agency. Clostridium difficile Section leads and partners infection. How to deal with the problem. Best Practice Guideline. 2008. 10. Owens RC Jr, Donskey CJ, Gaynes RP, et al. Antimicrobial-associated risk factors Incidence and mortality: H Roberts, WS Lim for Clostridium difficile infection. Clin Infect Dis 2008;46(Suppl 1):S19–31. Aetiology and epidemiology: M A Woodhead, R George 11. Tacconelli E, De Angelis G, Cataldo MA, et al. Does antibiotic exposure increase Clinical and radiological features: I Le Jeune, M Wani the risk of methicillin-resistant Staphylococcus aureus (MRSA) isolation? A systematic review and meta-analysis. J Antimicrob Chemother 2008;61:26–38. General investigations: I Le Jeune, M Wani 12. Trotter CL, Stuart JM, George R, et al. Increasing hospital admissions for Microbiological investigations: R George, W S Lim pneumonia, England. Emerg Infect Dis 2008;14:727–33. Severity assessment: W S Lim, H Roberts 13. Woodhead M, Welch CA, Harrison DA, et al. Community-acquired pneumonia on General management in hospital: A Hill, S Baudouin the intensive care unit: secondary analysis of 17,869 cases in the ICNARC Case Mix Programme Database. Crit Care 2006;10(Suppl 2):S1. Critical care issues: S Baudouin, A Hill 14. Royal College of Physicians. Acute medical care. The right person, in the right Antibiotic therapy: R Read, M A Woodhead, R George, J T setting – first time. Report of the Acute Medicine Task Force. London: Royal College Macfarlane of Physicians, 2007. http://thorax.bmj.com/ 15. Department of Health. The NHS Plan: a plan for investment, a plan for reform. Complications and failure to improve: H Roberts, W S Lim London: Department of Health, 2000. Primary care issues: M Levy, J T Macfarlane 16. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44(Suppl 2):S27–72. 11.3 Acknowledgements 17. Eccles M, Clapp Z, Grimshaw J, et al. North of England evidence based guidelines The Guidelines Development Committee would like to thank development project: methods of guideline development. BMJ 1996;312:760–2. many individuals and societies who have contributed to the 18. Sackett DL. Bias in analytic research. J Chronic Dis 1979;32:51–63. 19. Jaeschke R, Guyatt G, Sackett DL. Users’ guides to the medical literature. III. How development of this guideline. In particular, we thank Karen to use an article about a diagnostic test. A. Are the results of the study valid? on October 1, 2021 by guest. Protected copyright. McClean, Sue Allen, Elizabeth Hendron and Natalie Evidence-Based Medicine Working Group. JAMA 1994;271:389–91. Middlemore for organisational, administrative and library 20. Scottish Intercollegiate Guidelines Network. Clinical guidelines: criteria for appraisal. Edinburgh: Royal College of Physicians of Edinburgh, 1995. support; Dr Richard Bendall, Dr John Bremner, Dr Graham 21. Eddy DM. A manual for assessing health practices and designing practice policies. Douglas, Professor Paul Edelstein, Professor Roger Finch, Philadelphia: American College of Physicians, 1992. Rosalind Green, Dr Kieran Hand, Dr Elisabeth Ridgway, Dr 22. Guyatt GH, Sackett DL, Sinclair JC, et al. Users’ guides to the medical literature. IX. Martin Springsklee, Dr Kate Templeton, the Department of A method for grading health care recommendations. Evidence-Based Medicine Working Group. JAMA 1995;274:1800–4. Health Advisory Committee on Antimicrobial Resistance and 23. Woodhead MA, Macfarlane JT, McCracken JS, et al. Prospective study of the Healthcare Associated Infection, Joint Committee on aetiology and outcome of pneumonia in the community. Lancet 1987;1:671–4. Vaccination and Immunisation, Scottish Clinical Virology 24. Jokinen C, Heiskanen L, Juvonen H, et al. Incidence of community-acquired pneumonia in the population of four municipalities in eastern Finland. Am J Epidemiol Consultants Group and the UK Clinical Virology Network for 1993;137:977–88. constructive advice, comments and contributions received; Lisa 25. Foy HM, Cooney MK, Allan I, et al. Rates of pneumonia during influenza epidemics Stirk, Information Officer at the Centre for Reviews and in Seattle, 1964 to 1975. JAMA 1979;241:253–8. Dissemination, University of York for performing the literature 26. Macfarlane JT, Colville A, Guion A, et al. Prospective study of aetiology and outcome of adult lower-respiratory-tract infections in the community. Lancet searches; and Sally Welham, Deputy Chief Executive, British 1993;341:511–4. Thoracic Society for support and advice throughout the 27. Marrie TJ. Epidemiology of community-acquired pneumonia in the elderly. Semin guideline development process. Respir Infect 1990;5:260–8. 28. Lave JR, Fine MJ, Sankey SS, et al. Hospitalized pneumonia. Outcomes, treatment patterns, and costs in urban and rural areas. J Gen Intern Med 1996;11:415–21. 11.4 Declarations of interest 29. Marrie TJ, Carriere KC, Jin Y, et al. Factors associated with death among adults The committee members fulfilled the requirements of the BTS ,55 years of age hospitalized for community-acquired pneumonia. Clin Infect Dis 2003;36:413–21. regarding personal declaration of interests. Declaration of 30. Guest JF, Morris A. Community-acquired pneumonia: the annual cost to the interest forms were updated annually by committee members National Health Service in the UK. Eur Respir J 1997;10:1530–4.

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii45 BTS guidelines

31. Foy HM, Cooney MK, McMahan R, et al. Viral and mycoplasmal pneumonia in a 63. Reechaipichitkul W, Lulitanond V, Sawanyawisuth K, et al. Etiologies and Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from prepaid medical care group during an eight-year period. Am J Epidemiol treatment outcomes for out-patients with community-acquired pneumonia (CAP) at 1973;97:93–102. Srinagarind Hospital, Khon Kaen, Thailand. Southeast Asian J Trop Med Publ Health 32. Minogue MF, Coley CM, Fine MJ, et al. Patients hospitalized after initial outpatient 2005;36:1261–7. treatment for community-acquired pneumonia. Ann Emerg Med 1998;31:376–80. 64. Yen M-Y, Hu B-S, Chen Y-S, et al. A prospective etiologic study of community- 33. Torres A, Serra-Batlles J, Ferrer A, et al. Severe community-acquired pneumonia. acquired pneumonia in Taiwan. J Formosan Med Assoc 2005;104:724–30. Epidemiology and prognostic factors. Am Rev Respir Dis 1991;144:312–8. 65. Huang HH, Zhang YY, Xiu QY, et al. Community-acquired pneumonia in Shanghai, 34. Woodhead MA, Macfarlane JT, Rodgers FG, et al. Aetiology and outcome of China: microbial etiology and implications for empirical therapy in a prospective severe community-acquired pneumonia. J Infect 1985;10:204–10. study of 389 patients. Eur J Clin Microbiol Infect Dis 2006;25:369–74. 35. White RJ, Blainey AD, Harrison KJ, et al. Causes of pneumonia presenting to a 66. Saito A, Kohno S, Matsushima T, et al. Prospective multicenter study of the district general hospital. Thorax 1981;36:566–70. causative organisms of community-acquired pneumonia in adults in Japan. J Infect 36. Macfarlane JT, Finch RG, Ward MJ, et al. Hospital study of adult community- Chemother 2006;12:63–9. acquired pneumonia. Lancet 1982;2:255–8. 67. Lauderdale T-L, Chang F-Y, Ben R-J, et al. Etiology of community acquired 37. Lim WS, Macfarlane JT, Boswell TC, et al. Study of community acquired pneumonia pneumonia among adult patients requiring hospitalization in Taiwan. Respir Med aetiology (SCAPA) in adults admitted to hospital: implications for management 2005;99:1079–86. guidelines. Thorax 2001;56:296–301. 68. Paganin F, Lilienthal F, Bourdin A, et al. Severe community-acquired pneumonia: 38. Karalus NC, Cursons RT, Leng RA, et al. Community acquired pneumonia: aetiology assessment of microbial aetiology as mortality factor. Eur Respir J 2004;24:779–85. and prognostic index evaluation. Thorax 1991;46:413–8. 69. Venkatesan P, Gladman J, Macfarlane JT, et al. A hospital study of community 39. Lim I, Shaw DR, Stanley DP, et al. A prospective hospital study of the aetiology of acquired pneumonia in the elderly. Thorax 1990;45:254–8. community-acquired pneumonia. Med J Aust 1989;151:87–91. 70. Ausina V, Coll P, Sambeat M, et al. Prospective study on the etiology of 40. Mortensen EM, Kapoor WN, Chang C-CH, et al. Assessment of mortality after community-acquired pneumonia in children and adults in Spain. Eur J Clin Microbiol long-term follow-up of patients with community-acquired pneumonia. Clin Infect Dis Infect Dis 1988;7:342–7. 2003;37:1617–24. 71. Logroscino CD, Penza O, Locicero S, et al. Community-acquired pneumonia in 41. Yende S, Angus DC, Ali IS, et al. Influence of comorbid conditions on long-term adults: a multicentric observational AIPO study. Monaldi Arch Chest Dis mortality after pneumonia in older people. J Am Geriatr Soc 2007;55:518–25. 1999;54:11–7. 42. British Thoracic Society Research Committee and Public Health Laboratory 72. Leroy O, Vandenbussche C, Coffinier C, et al. Community-acquired aspiration Service. The aetiology, management and outcome of severe community-acquired pneumonia in intensive care units. Epidemiological and prognosis data. Am J Respir pneumonia on the intensive care unit. Respir Med 1992;86:7–13. Crit Care Med 1997;156:1922–9. 43. Alkhayer M, Jenkins PF, Harrison BD. The outcome of community acquired 73. Fernandez-Sabe N, Carratala J, Roson B, et al. Community-acquired pneumonia in pneumonia treated on the intensive care unit. Respir Med 1990;84:13–6. very elderly patients: causative organisms, clinical characteristics, and outcomes. Medicine 2003;82:159–69. 44. Moine P, Vercken JB, Chevret S, et al. Severe community-acquired pneumonia. 74. Ostergaard L, Andersen PL. Etiology of community-acquired pneumonia. Evaluation Etiology, epidemiology, and prognosis factors. French Study Group for Community- by transtracheal aspiration, blood culture, or serology. Chest 1993;104:1400–7. Acquired Pneumonia in the Intensive Care Unit. Chest 1994;105:1487–95. 75. Torres A, Dorca J, Zalacaı´n R , et al. Community-acquired pneumonia in chronic 45. Niederman MS, McCombs JS, Unger AN, et al. The cost of treating community- obstructive pulmonary disease: a Spanish multicenter study. Am J Respir Crit Care acquired pneumonia. Clin Ther 1998;20:820–37. Med 1996;154:1456–61. 46. Gilbert K, Gleason PP, Singer DE, et al. Variations in antimicrobial use and cost in 76. Marrie TJ. Bacteraemic pneumococcal pneumonia: a continuously evolving more than 2,000 patients with community-acquired pneumonia. Am J Med disease. J Infect 1992;24:247–55. 1998;104:17–27. 77. Marrie TJ, Durant H, Kwan C. Nursing home-acquired pneumonia. A case-control 47. Howard LSGE, Sillis M, Pasteur MC, et al. Microbiological profile of community- study. J Am Geriatr Soc 1986;34:697–702. acquired pneumonia in adults over the last 20 years. J Infect 2005;50:107–13. 78. Garb JL, Brown RB, Garb JR, et al. Differences in etiology of pneumonias in nursing 48. Lagerstrom F, Bader M, Foldevi M, et al. Microbiological etiology in clinically home and community patients. JAMA 1978;240:2169–72. diagnosed community-acquired pneumonia in primary care in Orebro, Sweden. Clin 79. Drinka PJ, Gauerke C, Voeks S, et al. Pneumonia in a nursing home. J Gen Intern Microbiol Infect 2003;9:645–52. Med 1994;9:650–2. 49. Ruiz M, Ewig S, Marcos MA, et al. Etiology of community-acquired pneumonia: 80. Lim WS, Macfarlane JT. A prospective comparison of nursing home acquired http://thorax.bmj.com/ impact of age, comorbidity, and severity. Am J Respir Crit Care Med pneumonia with community acquired pneumonia. Eur Respir J 2001;18:362–8. 1999;160:397–405. 81. Carratala J, Mykietiuk A, Fernandez-Sabe N, et al. Health care-associated 50. de Roux A, Ewig S, Garcia E, et al. Mixed community-acquired pneumonia in pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and hospitalised patients. Eur Respir J 2006;27:795–800. clinical outcomes. Arch Intern Med 2007;167:1393–9. 51. Gutierrez F, Masia M, Rodriguez JC, et al. Epidemiology of community-acquired 82. Sopena N, Sabria`-Leal M, Pedro-Botet ML, et al. Comparative study of the clinical pneumonia in adult patients at the dawn of the 21st century: a prospective study on presentation of Legionella pneumonia and other community-acquired pneumonias. the Mediterranean coast of Spain. Clin Microbiol Infect 2005;11:788–800. Chest 1998;113:1195–200. 52. Fernandez Alvarez R, Suarez Toste I, Rubinos Cuadrado G, et al. Community- 83. de Roux A, Cavalcanti M, Marcos MA, et al. Impact of alcohol abuse in the etiology acquired pneumonia: aetiologic changes in a limited geographic area. An 11-year and severity of community-acquired pneumonia. Chest 2006;129:1219–25. prospective study. Eur J Clin Microbiol Infect Dis 2007;26:495–9. 84. Stout JE, Yu VL. Legionellosis. N Engl J Med 1997;337:682–7. 53. Arnold FW, Summersgill JT, Lajoie AS, et al. A worldwide perspective of atypical 85. Mier L, Dreyfuss D, Darchy B, et al. Is penicillin G an adequate initial treatment for on October 1, 2021 by guest. Protected copyright. pathogens in community-acquired pneumonia. Am J Respir Crit Care Med aspiration pneumonia? A prospective evaluation using a protected specimen brush 2007;175:1086–93. and quantitative cultures. Intensive Care Med 1993;19:279–84. 54. Ngeow Y-F, Suwanjutha S, Chantarojanasriri T, et al. An Asian study on the 86. de Roux A, Marcos MA, Garcia E, et al. Viral community-acquired pneumonia in prevalence of atypical respiratory pathogens in community-acquired pneumonia. nonimmunocompromised adults. Chest 2004;125:1343–51. Int J Infect Dis 2005;9:144–53. 87. Kim PE, Musher DM, Glezen WP, et al. Association of invasive pneumococcal 55. Diaz A, Barria P, Niederman M, et al. Etiology of community-acquired pneumonia in disease with season, atmospheric conditions, air pollution, and the isolation of hospitalized patients in Chile: the increasing prevalence of respiratory viruses among respiratory viruses. Clin Infect Dis 1996;22:100–6. classic pathogens. Chest 2007;131:779–87. 88. Mercat A, Nguyen J, Dautzenberg B. An outbreak of pneumococcal pneumonia in 56. Matute AJ, Brouwer WP, Hak E, et al. Aetiology and resistance patterns of two men’s shelters. Chest 1991;99:147–51. community-acquired pneumonia in Leon, Nicaragua. Int J Antimicrob Agents 89. Naik FC, Ricketts KD, Harrison TG, et al. Legionnaires’ disease in England and 2006;28:423–7. Wales (1995–2005). Health Protection Report 2008. 2008. 57. Nagalingam NA, Adesiyun AA, Swanston WH, et al. Seroprevalence of Legionella 90. Newton LH, Joseph CA, Hutchinson EJ, et al. Legionnaires’ disease surveillance: pneumophila in pneumonia patients in four major hospitals in Trinidad and Tobago. England and Wales, 1995. Commun Dis Rep CDR Rev 1996;6:R151–5. West Indian Med J 2005;54:375–8. 91. Joseph CA, Harrison TG, Ilijic-Car D, et al. Legionnaires’ disease in residents of 58. Chedid MBF, Ilha DdO, Chedid MF, et al. Community-acquired pneumonia by England and Wales: 1998. Commun Dis Public Health 1999;2:280–4. Legionella pneumophila serogroups 1–6 in Brazil. Respir Med 2005;99:966–75. 92. Joseph CA, Harrison TG, Ilijic-Car D, et al. Legionnaires’ disease in residents of 59. Marrie TJ, Peeling RW, Reid T, et al. Chlamydia species as a cause of community- England and Wales: 1996. Commun Dis Rep CDR Rev 1997;7:R153–9. acquired pneumonia in Canada. Eur Respir J 2003;21:779–84. 93. Saikku P, Wang SP, Kleemola M, et al. An epidemic of mild pneumonia due to an 60. Valdivia L, Nix D, Wright M, et al. Coccidioidomycosis as a common cause of unusual strain of Chlamydia psittaci. J Infect Dis 1985;151:832–9. community-acquired pneumonia [correction appears in Emerg Infect Dis 94. Kleemola M, Saikku P, Visakorpi R, et al. Epidemics of pneumonia caused by 2006;12:1307]. Emerg Infect Dis 2006;12:958–62. TWAR, a new Chlamydia organism, in military trainees in Finland. J Infect Dis 61. Wattanathum A, Chaoprasong C, Nunthapisud P, et al. Community-acquired 1988;157:230–6. pneumonia in southeast Asia: the microbial differences between ambulatory and 95. Troy CJ, Peeling RW, Ellis AG, et al. Chlamydia pneumoniae as a new source of hospitalized patients. Chest 2003;123:1512–9. infectious outbreaks in nursing homes. JAMA 1997;277:1214–8. 62. Bansal S, Kashyap S, Pal LS, et al. Clinical and bacteriological profile of community 96. Wellinghausen N, Straube E, Freidank H, et al. Low prevalence of Chlamydia acquired pneumonia in Shimla, Himachal Pradesh. Indian J Chest Dis Allied Sci pneumoniae in adults with community-acquired pneumonia. Int J Med Microbiol 2004;46:17–22. 2006;296:485–91. iii46 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

97. Steinhoff D, Lode H, Ruckdeschel G, et al. Chlamydia pneumoniae as a cause of 126. Connolly AM, Salmon RL, Lervy B, et al. What are the complications of influenza Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from community-acquired pneumonia in hospitalized patients in Berlin. Clin Infect Dis and can they be prevented? Experience from the 1989 epidemic of H3N2 influenza A 1996;22:958–64. in general practice. BMJ 1993;306:1452–4. 98. Lieberman D, Ben-Yaakov M, Lazarovich Z, et al. Chlamydia pneumoniae 127. Farr BM, Kaiser DL, Harrison BD, et al. Prediction of microbial aetiology at community-acquired pneumonia: a review of 62 hospitalized adult patients. Infection admission to hospital for pneumonia from the presenting clinical features. British 1996;24:109–14. Thoracic Society Pneumonia Research Subcommittee. Thorax 1989;44:1031–5. 99. Kauppinen MT, Saikku P, Kujala P, et al. Clinical picture of community-acquired 128. Fang GD, Fine M, Orloff J, et al. New and emerging etiologies for community- Chlamydia pneumoniae pneumonia requiring hospital treatment: a comparison acquired pneumonia with implications for therapy. A prospective multicenter study between chlamydial and pneumococcal pneumonia. Thorax 1996;51:185–9. of 359 cases. Medicine (Baltimore) 1990;69:307–16. 100. Wreghitt T. Chlamydial infection of the respiratory tract. Commun Dis Rep CDR Rev 129. Riquelme R, Torres A, El-Ebiary M, et al. Community-acquired pneumonia in the 1993;3:R119–24. elderly: a multivariate analysis of risk and prognostic factors. Am J Respir Crit Care 101. Pebody RG, Wall PG, Ryan MJ, et al. Epidemiological features of Coxiella burnetii Med 1996;154:1450–5. infection in England and Wales: 1984 to 1994. Commun Dis Rep CDR Rev 130. Bohte R, Hermans J, van den Broek PJ. Early recognition of Streptococcus 1996;6:R128–32. pneumoniae in patients with community-acquired pneumonia. Eur J Clin Microbiol 102. McNabb WR, Shanson DC, Williams TD, et al. Adult community-acquired Infect Dis 1996;15:201–5. pneumonia in central London. J R Soc Med 1984;77:550–5. 131. Helms CM, Wintermeyer LA, Zeitler RR, et al. An outbreak of community-acquired 103. Hirani NA, Macfarlane JT. Impact of management guidelines on the outcome of Legionnaires’ disease pneumonia. Am J Public Health 1984;74:835–6. severe community acquired pneumonia. Thorax 1997;52:17–21. 132. Granados A, Podzamczer D, Gudiol F, et al. Pneumonia due to Legionella 104. Rotas M, McCalla S, Liu C, et al. Methicillin-resistant Staphylococcus aureus pneumophila and pneumococcal pneumonia: similarities and differences on necrotizing pneumonia arising from an infected episiotomy site. Obstet Gynecol presentation. Eur Respir J 1989;2:130–4. 2007;109:533–6. 133. Fernandez-Sabe N, Roson B, Carratala J, et al. Clinical diagnosis of Legionella 105. Asnis D, Haralambou G, Tawiah P, et al. Methicillin-resistant Staphylococcus pneumonia revisited: evaluation of the Community-Based Pneumonia Incidence aureus necrotizing pneumonia arising from an infected episiotomy site. Obstet Study Group scoring system. Clin Infect Dis 2003;37:483–9. Gynecol 2007;110:188. 134. Lieberman D, Porath A, Schlaeffer F, et al. Legionella species community-acquired 106. Garnier F, Tristan A, Francois B, et al. Pneumonia and new methicillin-resistant pneumonia. A review of 56 hospitalized adult patients. Chest 1996;109:1243–9. Staphylococcus aureus clone. Emerg Infect Dis 2006;12:498–500. 135. Falco´V,Ferna´ndez de Sevilla T, Alegre J, et al. Legionella pneumophila. A cause of 107. Nimmo GR, Playford EG. Community-acquired MRSA bacteraemia: four additional severe community-acquired pneumonia. Chest 1991;100:1007–11. cases including one associated with severe pneumonia. Med J Aust 2003;178:245. 136. Helms CM, Viner JP, Sturm RH, et al. Comparative features of pneumococcal, mycoplasmal, and Legionnaires’ disease pneumonias. 108. Peleg AY, Munckhof WJ. Fatal necrotising pneumonia due to community-acquired Ann Intern Med 1979;90:543–7. methicillin-resistant Staphylococcus aureus (MRSA). Med J Aust 2004;181:228–9. 137. Marrie TJ. Mycoplasma pneumoniae pneumonia requiring hospitalization, with 109. Risson DC, O’Connor ED, Guard RW, et al. A fatal case of necrotising pneumonia emphasis on infection in the elderly. Arch Intern Med 1993;153:488–94. due to community-associated methicillin-resistant Staphylococcus aureus. 138. Puljiz I, Kuzman I, Dakovic-Rode O, et al. Chlamydia pneumoniae and Mycoplasma Med J Aust 2007;186:479–80. pneumoniae pneumonia: comparison of clinical, epidemiological characteristics and 110. Vayalumkal JV, Whittingham H, Vanderkooi O, et al. Necrotizing pneumonia and laboratory profiles. Epidemiol Infect 2006;134:548–55. septic shock: suspecting CA-MRSA in patients presenting to Canadian emergency 139. File TM Jr, Plouffe JF Jr, Breiman RF, et al. Clinical characteristics of Chlamydia departments. CJEM Can J Emerg Med Care 2007;9:300–3. pneumoniae infection as the sole cause of community-acquired pneumonia. Clin 111. Monaco M, Antonucci R, Palange P, et al. Methicillin-resistant Staphylococcus Infect Dis 1999;29:426–8. aureus necrotizing pneumonia. Emerg Infect Dis 2005;11:1647–8. 140. Lieberman D, Boldur I, Manor E, et al. Q-fever pneumonia in the Negev region of 112. Torell E, Molin D, Tano E, et al. Community-acquired pneumonia and bacteraemia in Israel: a review of 20 patients hospitalised over a period of one year. J Infect a healthy young woman caused by methicillin-resistant Staphylococcus aureus 1995;30:135–40. (MRSA) carrying the genes encoding Panton-Valentine leukocidin (PVL). 141. Goyette M, Bouchard J, Poirier A, et al. Importance of Q fever in community Scand J Infect Dis 2005;37:902–4. acquired pneumonia. Can J Infect Dis 1996;7:370–3. 113. Soderquist B, Berglund C, Stralin K. Community-acquired pneumonia and 142. Sobradillo V, Ansola P, Baranda F, et al. Q fever pneumonia: a review of 164

bacteremia caused by an unusual methicillin-resistant Staphylococcus aureus community-acquired cases in the Basque country. Eur Respir J 1989;2:263–6. http://thorax.bmj.com/ (MRSA) strain with sequence type 36, staphylococcal cassette chromosome mec 143. Caron F, Meurice JC, Ingrand P, et al. Acute Q fever pneumonia: a review of 80 type IV and Panton-Valentine leukocidin genes. Eur J Clin Microbiol Infect Dis hospitalized patients. Chest 1998;114:808–13. 2006;25:604–6. 144. Feldman C, Kallenbach JM, Levy H, et al. Comparison of bacteraemic community- 114. Magira EE, Zervakis D, Routsi C, et al. Community-acquired methicillin-resistant acquired lobar pneumonia due to Streptococcus pneumoniae and Klebsiella Staphylococcus aureus carrying Panton-Valentine leukocidin genes: a lethal cause of pneumoniae in an intensive care unit. Respiration 1991;58:265–70. pneumonia in an adult immunocompetent patient. Scand J Infect Dis 2007;39:466–9. 145. Rudin ML, Michael JR, Huxley EJ. Community-acquired acinetobacter pneumonia. 115. Klein JL, Petrovic Z, Treacher D, et al. Severe community-acquired pneumonia Am J Med 1979;67:39–43. caused by Panton-Valentine leukocidin-positive Staphylococcus aureus: first 146. Henderson A, Wall D. Streptococcus milleri liver abscess presenting as fulminant reported case in the United Kingdom. Intensive Care Med 2003;29:1399. pneumonia. Aust N Z J Surg 1993;63:237–40.

116. Honarpour N, Mao JT. A Case of fatal community-acquired necrotizing pneumonia 147. Goolam MA, Feldman C, Smith C, et al. Does primary Streptococcus viridans on October 1, 2021 by guest. Protected copyright. caused by panton-valentine leukocidin positive methicillin-sensitive Staphylococcus pneumonia exist? S Afr Med J 1992;82:432–4. aureus. Curr Respir Med Rev 2007;3:49–51. 148. Marrie TJ. Pneumonia in the elderly. Curr Opin Pulm Med 1996;2:192–7. 117. Beilouny B, Ciupea A, Eloy C, et al. Fatal community-acquired pneumonia due to 149. Metlay JP, Schulz R, Li YH, et al. Influence of age on symptoms at presentation in Staphylococcus aureus carrying Panton-Valentine leukocidin genes after a stay in patients with community-acquired pneumonia. Arch Intern Med 1997;157:1453–9. Africa. Intensive Care Med 2008;34:388–9. 150. Riquelme R, Torres A, el-Ebiary M, et al. Community-acquired pneumonia in the 118. Baldwin LN, Lowe AD. Panton-Valentine Leukocidin associated with community elderly. Clinical and nutritional aspects. Am J Respir Crit Care Med acquired methicillin resistant Staphylococcus aureus: a case report and review of 1997;156:1908–14. interim guidelines. Anaesthesia 2008;63:764–6. 151. Marrie TJ, Haldane EV, Faulkner RS, et al. Community-acquired pneumonia 119. Francis JS, Doherty MC, Lopatin U, et al. Severe community-onset pneumonia in requiring hospitalization. Is it different in the elderly? J Am Geriatr Soc healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the 1985;33:671–80. Panton-Valentine leukocidin genes. Clin Infect Dis 2005;40:100–7. 152. Kikuchi R, Watabe N, Konno T, et al. High incidence of silent aspiration in elderly 120. Hageman JC, Uyeki TM, Francis JS, et al. Severe community-acquired pneumonia patients with community-acquired pneumonia. Am J Respir Crit Care Med due to Staphylococcus aureus, 2003–04 influenza season. Emerg Infect Dis 1994;150:251–3. 2006;12:894–9. 153. Marrie TJ, Blanchard W. A comparison of nursing home-acquired pneumonia 121. Chua AP, Lee KH. Fatal bacteraemic pneumonia due to community-acquired patients with patients with community-acquired pneumonia and nursing home methicillin-resistant Staphylococcus aureus. Singapore Med J 2006;47:546–8. patients without pneumonia. J Am Geriatr Soc 1997;45:50–5. 122. Anon. Severe methicillin-resistant Staphylococcus aureus community-acquired 154. Reza Shariatzadeh M, Huang JQ, Marrie TJ. Differences in the features of pneumonia associated with influenza – Louisiana and Georgia, December 2006– aspiration pneumonia according to site of acquisition: community or continuing care January 2007. MMWR – Morbidity & Mortality Weekly Report 2007;56:325–9. facility. J Am Geriatr Soc 2006;54:296–302. 123. Hyvernat H, Pulcini C, Carles D, et al. Fatal Staphylococcus aureus haemorrhagic 155. Bartlett JG, Gorbach SL, Finegold SM. The bacteriology of aspiration pneumonia. pneumonia producing Panton-Valentine leucocidin. Scand J Infect Dis 2007;39:183–5. Am J Med 1974;56:202–7. 124. Balis E, Diacaki C, Tselioti P, et al. Community-acquired pneumonia and bacteremia 156. Marik PE, Careau P. The role of anaerobes in patients with ventilator-associated due to methicillin-resistant Staphylococcus aureus carrying Panton-Valentine- pneumonia and aspiration pneumonia: a prospective study. Chest 1999;115:178–83. leukocidin gene in Greece: two case reports and literature review. J Chemother 157. El-Solh AA, Pietrantoni C, Bhat A, et al. Microbiology of severe aspiration 2007;19:703–8. pneumonia in institutionalized elderly. Am J Respir Crit Care Med 2003;167:1650–4. 125. Hutchinson EJ, Joseph CA, Zambon M, et al. Influenza surveillance in England and 158. Ott SR, Allewelt M, Lorenz J, et al. Moxifloxacin vs ampicillin/sulbactam in Wales: October 1995 to June 1996. Commun Dis Rep CDR Rev 1996;6:R163–9. aspiration pneumonia and primary lung abscess. Infection 2008;36:23–30.

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii47 BTS guidelines

159. Metlay JP, Kapoor WN, Fine MJ. Does this patient have community-acquired 192. Mene´ndezR, Co´rdoba J, de La Cuadra P, et al. Value of the polymerase chain Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from pneumonia? Diagnosing pneumonia by history and physical examination. JAMA reaction assay in noninvasive respiratory samples for diagnosis of community- 1997;278:1440–5. acquired pneumonia. Am J Respir Crit Care Med 1999;159:1868–73. 160. Metlay JP, Fine MJ. Testing strategies in the initial management of patients with 193. Ewig S, Bauer T, Hasper E, et al. Value of routine microbial investigation in community-acquired pneumonia. Ann Intern Med 2003;138:109–18. community-acquired pneumonia. Can J Infect Dis 1996;63:169. 161. Spiteri MA, Cook DG, Clarke SW. Reliability of eliciting physical signs in 194. Woodhead MA, Arrowsmith J, Chamberlain-Webber R, et al. The value of routine examination of the chest. Lancet 1988;1:873–5. microbial investigation in community-acquired pneumonia. Respir Med 162. Melbye H, Straume B, Aasebø U, et al. The diagnosis of adult pneumonia in general 1991;85:313–7. practice. The diagnostic value of history, physical examination and some blood tests. 195. van der Eerden MM, Vlaspolder F, de Graaff CS, et al. Value of intensive Scand J Prim Health Care 1988;6:111–7. diagnostic microbiological investigation in low- and high-risk patients with 163. Diehr P, Wood RW, Bushyhead J, et al. Prediction of pneumonia in outpatients with community-acquired pneumonia. Eur J Clin Microbiol Infect Dis 2005;24:241–9. acute cough—a statistical approach. J Chronic Dis 1984;37:215–25. 196. Hohenthal U, Vainionpaa R, Meurman O, et al. Aetiological diagnosis of community 164. O’Brien WT Sr, Rohweder DA, Lattin GE Jr, et al. Clinical indicators of radiographic acquired pneumonia: utility of rapid microbiological methods with respect to disease findings in patients with suspected community-acquired pneumonia: who needs a severity. Scand J Infect Dis 2008;40:131–8. chest x-ray? [correction appears in J Am Coll Radiol 2006;3:A4]. J Am Coll Radiol 197. Templeton KE, Scheltinga SA, van den Eeden WCJFM, et al. Improved diagnosis of 2006;3:703–6. the etiology of community-acquired pneumonia with real-time polymerase chain 165. Macfarlane J, Holmes W, Gard P, et al. Prospective study of the incidence, reaction. Clin Infect Dis 2005;41:345–51. aetiology and outcome of adult lower respiratory tract illness in the community. 198. Theerthakarai R, El-Halees W, Ismail M, et al. Nonvalue of the initial Thorax 2001;56:109–14. microbiological studies in the management of nonsevere community-acquired 166. Macfarlane JT, Miller AC, Roderick Smith WH, et al. Comparative radiographic pneumonia. Chest 2001;119:181–4. features of community acquired Legionnaires’ disease, pneumococcal pneumonia, 199. Ewig S, Schlochtermeier M, Goke N, et al. Applying sputum as a diagnostic tool in mycoplasma pneumonia, and psittacosis. Thorax 1984;39:28–33. pneumonia: limited yield, minimal impact on treatment decisions. Chest 167. Kauppinen MT, La¨hde S, Syrja¨la¨ H. Roentgenographic findings of pneumonia 2002;121:1486–92. caused by Chlamydia pneumoniae. A comparison with streptococcus pneumonia. 200. Waterer GW, Wunderink RG. The influence of the severity of community-acquired Arch Intern Med 1996;156:1851–6. pneumonia on the usefulness of blood cultures. Respir Med 2001;95:78–82. 168. Gikas A, Kofteridis D, Bouros D, et al. Q fever pneumonia: appearance on chest 201. Campbell SG, Marrie TJ, Anstey R, et al. The contribution of blood cultures to the radiographs. Radiology 1999;210:339–43. clinical management of adult patients admitted to the hospital with community- 169. Marrie TJ, Peeling RW, Fine MJ, et al. Ambulatory patients with community- acquired pneumonia: a prospective observational study. Chest 2003;123:1142–50. acquired pneumonia: the frequency of atypical agents and clinical course. Am J Med 202. Woodhead M, Macfarlane J. Local antibiotic guidelines for adult community- 1996;101:508–15. acquired pneumonia (CAP): a survey of UK hospital practice in 1999. J Antimicrob 170. Macfarlane J, Rose D. Radiographic features of staphylococcal pneumonia in Chemother 2000;46:141–3. adults and children. Thorax 1996;51:539–40. 203. Chambers DC, Waterer GW. Are blood cultures necessary in community-acquired 171. Korvick JA, Hackett AK, Yu VL, et al. Klebsiella pneumonia in the modern era: pneumonia? Clin Pulmon Med 2005;12:146–52. clinicoradiographic correlations. South Med J 1991;84:200–4. 204. Benenson RS, Kepner AM, Pyle DN 2nd, et al. Selective use of blood cultures in 172. Syrja¨la¨H,Broas M, Suramo I, et al. High-resolution computed tomography for the emergency department pneumonia patients. J Emerg Med 2007;33:1–8. diagnosis of community-acquired pneumonia. Clin Infect Dis 1998;27:358–63. 205. Ramanujam P, Rathlev NK. Blood cultures do not change management in 173. Reittner P, Mu¨ller NL, Heyneman L, et al. Mycoplasma pneumoniae pneumonia: hospitalized patients with community-acquired pneumonia. Acad Emerg Med radiographic and high-resolution CT features in 28 patients. AJR Am J Roentgenol 2006;13:740–5. 2000;174:37–41. 206. Corbo J, Friedman B, Bijur P, et al. Limited usefulness of initial blood cultures in 174. Beall DP, Scott WW Jr, Kuhlman JE, et al. Utilization of computed tomography in community acquired pneumonia. Emerg Med J 2004;21:446–8. patients hospitalized with community-acquired pneumonia. Md Med J 207. Bartlett JG, Dowell SF, Mandell LA, et al. Practice guidelines for the management 1998;47:182–7. of community-acquired pneumonia in adults. Infectious Diseases Society of America. 175. Tanaka N, Matsumoto T, Kuramitsu T, et al. High resolution CT findings in Clin Infect Dis 2000;31:347–82. community-acquired pneumonia. J Comput Assist Tomogr 1996;20:600–8. 176. Mittl RL Jr, Schwab RJ, Duchin JS, et al. Radiographic resolution of community- 208. Taylor EL, Marrie TJ, Fine MJ, et al. Observations from a multicentre study on the http://thorax.bmj.com/ acquired pneumonia. Am J Respir Crit Care Med 1994;149(3 Pt 1):630–5. use of the sputum specimen in patients hospitalized with community-acquired 177. El Solh AA, Aquilina AT, Gunen H, et al. Radiographic resolution of community- pneumonia. Can J Infect Dis 1999;10:39–46. acquired bacterial pneumonia in the elderly. J Am Geriatr Soc 2004;52:224–9. 209. Reed WW, Byrd GS, Gates RH Jr, et al. Sputum gram’s stain in community-acquired 178. Bruns AHW, Oosterheert JJ, Prokop M, et al. Patterns of resolution of chest pneumococcal pneumonia. A meta-analysis. West J Med 1996;165:197–204. radiograph abnormalities in adults hospitalized with severe community-acquired 210. Rein MF, Gwaltney JM Jr, O’Brien WM, et al. Accuracy of Gram’s stain in pneumonia. Clin Infect Dis 2007;45:983–91. identifying pneumococci in sputum. JAMA 1978;239:2671–3. 179. Jay SJ, Johanson WG Jr, Pierce AK. The radiographic resolution of Streptococcus 211. Garcia-Vazquez E, Marcos MA, Mensa J, et al. Assessment of the usefulness of pneumoniae pneumonia. N Engl J Med 1975;293:798–801. sputum culture for diagnosis of community-acquired pneumonia using the PORT 180. Granet KM, Wallach SL, Horvath K, et al. Chest radiographs in patients with predictive scoring system. Arch Intern Med 2004;164:1807–11. community-acquired pneumonia. N J Med 1996;93:37–41. 212. Miyashita N, Shimizu H, Ouchi K, et al. Assessment of the usefulness of sputum 181. Holmberg H, Kragsbjerg P. Association of pneumonia and lung cancer: the value of Gram stain and culture for diagnosis of community-acquired pneumonia requiring on October 1, 2021 by guest. Protected copyright. convalescent chest radiography and follow-up. Scand J Infect Dis 1993;25:93–100. hospitalization. Med Sci Monit 2008;14:CR171–6. 182. Gibson SP, Weir DC, Burge PS. A prospective audit of the value of fibre optic 213. Fine MJ, Orloff JJ, Rihs JD, et al. Evaluation of housestaff physicians’ preparation bronchoscopy in adults admitted with community acquired pneumonia. Respir Med and interpretation of sputum Gram stains for community-acquired pneumonia. J Gen 1993;87:105–9. Intern Med 1991;6:189–98. 183. British Thoracic Society. BTS guideline for emergency oxygen use in adult 214. Croce MA, Fabian TC, Waddle-Smith L, et al. Utility of Gram’s stain and efficacy of patients. Thorax 2008;63(Suppl 6):vi1–68. quantitative cultures for posttraumatic pneumonia: a prospective study. Ann Surg 184. Holmberg H, Bodin L, Jo¨nsson I, et al. Rapid aetiological diagnosis of pneumonia 1998;227:743–55. based on routine laboratory features. Scand J Infect Dis 1990;22:537–45. 215. Roberts ME, Macfarlane JT, George RC, et al. Microbiology investigations in 185. Castro-Guardiola A, Armengou-Arxe A, Viejo-Rodriguez A, et al. Differential community acquired pneumonia—most laboratories in England and Wales do not diagnosis between community-acquired pneumonia and non-pneumonia diseases of offer all those recommended in the British Thoracic Society guideline. J Infect the chest in the emergency ward. Eur J Intern Med 2000;11:334–9. 2008;56:291–4. 186. Smith RP, Lipworth BJ, Cree IA, et al. C-reactive protein. A clinical marker in 216. Venkatesan P, Macfarlane JT. Role of pneumococcal antigen in the diagnosis of community-acquired pneumonia. Chest 1995;108:1288–91. pneumococcal pneumonia. Thorax 1992;47:329–31. 187. Hansson LO, Hedlund JU, Ortqvist AB. Sequential changes of inflammatory and 217. Murdoch DR, Laing RT, Mills GD, et al. Evaluation of a rapid nutritional markers in patients with community-acquired pneumonia. Scand J Clin immunochromatographic test for detection of Streptococcus pneumoniae antigen in Lab Invest 1997;57:111–8. urine samples from adults with community-acquired pneumonia. J Clin Microbiol 188. Flanders SA, Stein J, Shochat G, et al. Performance of a bedside C-reactive protein 2001;39:3495–8. test in the diagnosis of community-acquired pneumonia in adults with acute cough. 218. Andreo F, Dominguez J, Ruiz J, et al. Impact of rapid urine antigen tests to Am J Med 2004;116:529–35. determine the etiology of community-acquired pneumonia in adults. Respiratory 189. Ortqvist A, Hedlund J, Wretlind B, et al. Diagnostic and prognostic value of Medicine 2006;100:884–91. interleukin-6 and C-reactive protein in community-acquired pneumonia. Scand J Infect 219. Briones ML, Blanquer J, Ferrando D, et al. Assessment of analysis of urinary Dis 1995;27:457–62. pneumococcal antigen by immunochromatography for etiologic diagnosis of 190. Garcia Vazquez E, Martinez JA, Mensa J, et al. C-reactive protein levels in community-acquired pneumonia in adults. Clin Vaccine Immunol 2006;13:1092–7. community-acquired pneumonia. Eur Respir J 2003;21:702–5. 220. Gutierrez F, Masia M, Rodriguez JC, et al. Evaluation of the 191. Sanyal S, Smith PR, Saha AC, et al. Initial microbiologic studies did not affect immunochromatographic Binax NOW assay for detection of Streptococcus outcome in adults hospitalized with community-acquired pneumonia. Am J Respir pneumoniae urinary antigen in a prospective study of community-acquired Crit Care Med 1999;160:346–8. pneumonia in Spain. Clin Infect Dis 2003;36:286–92. iii48 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

221. Kobashi Y, Yoshida K, Miyashita N, et al. Evaluating the use of a Streptococcus 251. Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from pneumoniae urinary antigen detection kit for the management of community- with community-acquired pneumonia. N Engl J Med 1997;336:243–50. acquired pneumonia in Japan. Respiration 2007;74:387–93. 252. Ortqvist A, Hedlund J, Grillner L, et al. Aetiology, outcome and prognostic factors 222. Lasocki S, Scanvic A, Le Turdu F, et al. Evaluation of the Binax NOW Streptococcus in community-acquired pneumonia requiring hospitalization. Eur Respir J pneumoniae urinary antigen assay in intensive care patients hospitalized for 1990;3:1105–13. pneumonia. Intensive Care Med 2006;32:1766–72. 253. Garcia-Ordonez MA, Garcia-Jimenez JM, Paez F, et al. Clinical aspects and 223. Smith MD, Derrington P, Evans R, et al. Rapid diagnosis of bacteremic prognostic factors in elderly patients hospitalised for community-acquired pneumococcal infections in adults by using the Binax NOW Streptococcus pneumonia. Eur J Clin Microbiol Infect Dis 2001;20:14–9. pneumoniae urinary antigen test: a prospective, controlled clinical evaluation. J Clin 254. van Eeden SF, Coetzee AR, Joubert JR. Community-acquired pneumonia—factors Microbiol 2003;41:2810–3. influencing intensive care admission. S Afr Med J 1988;73:77–81. 224. Porcel JM, Ruiz-Gonzalez A, Falguera M, et al. Contribution of a pleural antigen 255. Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired assay (Binax NOW) to the diagnosis of pneumococcal pneumonia. Chest pneumonia severity on presentation to hospital: an international derivation and 2007;131:1442–7. validation study. Thorax 2003;58:377–82. 225. Sheppard CL, Harrison TG, Kearns AM, et al. Diagnosis of invasive pneumococcal 256. Go´mezJ, Ban˜os V, Ruiz Go´mez J, et al. Prospective study of epidemiology and infection by PCR amplification of Streptococcus pneumoniae genomic fragments in prognostic factors in community-acquired pneumonia. Eur J Clin Microbiol Infect Dis blood: a multi-centre comparative study. Commun Dis Public Health 2003;6:221–7. 1996;15:556–60. 226. Murdoch DR, Anderson TP, Beynon KA, et al. Evaluation of a PCR assay for 257. Chalmers JD, Singanayagam A, Hill AT. C-reactive protein is an independent detection of Streptococcus pneumoniae in respiratory and nonrespiratory samples predictor of severity in community-acquired pneumonia. Am J Med from adults with community-acquired pneumonia. J Clin Microbiol 2003;41:63–6. 2008;121:219–25. 227. Birtles RJ, Harrison TG, Samuel D, et al. Evaluation of urinary antigen ELISA for 258. Leroy O, Georges H, Beuscart C, et al. Severe community-acquired pneumonia in diagnosing Legionella pneumophila serogroup 1 infection. J Clin Pathol ICUs: prospective validation of a prognostic score. Intensive Care Med 1990;43:685–90. 1996;22:1307–14. 228. Lettinga KD, Verbon A, Weverling GJ, et al. Legionnaires’ disease at a Dutch flower 259. Hasley PB, Albaum MN, Li YH, et al. Do pulmonary radiographic findings at show: prognostic factors and impact of therapy. Emerg Infect Dis 2002;8:1448–54. presentation predict mortality in patients with community-acquired pneumonia? 229. Helbig JH, Uldum So A, Bernander S, et al. Clinical utility of urinary antigen Arch Intern Med 1996;156:2206–12. detection for diagnosis of community-acquired, travel-associated, and nosocomial 260. Feldman C, Kallenbach JM, Levy H, et al. Community-acquired pneumonia of Legionnaires’ disease. J Clin Microbiol 2003;41:838–40. diverse aetiology: prognostic features in patients admitted to an intensive care unit 230. Boswell TC, Marshall LE, Kudesia G. False-positive legionella titres in routine and a ‘‘severity of illness’’ core. Intensive Care Med 1989;15:302–7. clinical serology testing detected by absorption with campylobacter: implications for 261. Hedlund J, Hansson LO. Procalcitonin and C-reactive protein levels in community- the serological diagnosis of legionnaires’ disease. J Infect 1996;32:23–6. acquired pneumonia: correlation with etiology and prognosis. Infection 231. Medical Devices Agency. Mycoplasma pneumoniae antibody assays. Medical 2000;28:68–73. Devices Agency Evaluation Report MDA/98/62, 1998. 262. Masia M, Gutierrez F, Shum C, et al. Usefulness of procalcitonin levels in 232. Beersma MF, Dirven K, van Dam AP, et al. Evaluation of 12 commercial tests and community-acquired pneumonia according to the patients’ outcome research team the complement fixation test for Mycoplasma pneumoniae-specific immunoglobulin pneumonia severity index. Chest 2005;128:2223–9. G (IgG) and IgM antibodies, with PCR used as the ‘‘gold standard’’. J Clin Microbiol 263. Boussekey N, Leroy O, Alfandari S, et al. Procalcitonin kinetics in the prognosis of 2005;43:2277–85. severe community-acquired pneumonia. Intensive Care Med 2006;32:469–72. 233. Daxboeck F, Khanakah G, Bauer C, et al. Detection of Mycoplasma pneumoniae 264. Kruger S, Ewig S, Marre R, et al. Procalcitonin predicts patients at low risk of death in serum specimens from patients with mycoplasma pneumonia by PCR from community-acquired pneumonia across all CRB-65 classes. Eur Respir J [correction appears in Int J Med Microbiol 2006;296:55]. Int J Med Microbiol 2008;31:349–55. 2005;295:279–85. 265. Boussekey N, Leroy O, Georges H, et al. Diagnostic and prognostic values of 234. Sillis M, White P, Caul EO, et al. The differentiation of Chlamydia species by antigen admission procalcitonin levels in community-acquired pneumonia in an intensive detection in sputum specimens from patients with community-acquired acute care unit. Infection 2005;33:257–63. respiratory infections. J Infect 1992;25(Suppl 1):77–86. 266. Tejera A, Santolaria F, Diez ML, et al. Prognosis of community acquired pneumonia 235. Garnett P, Brogan O, Lafong C, et al. Comparison of throat swabs with sputum (CAP): value of triggering receptor expressed on myeloid cells-1 (TREM-1) and other specimens for the detection of Chlamydia pneumoniae antigen by direct mediators of the inflammatory response. Cytokine 2007;38:117–23. http://thorax.bmj.com/ immunofluorescence. J Clin Pathol 1998;51:309–11. 267. Aalto H, Takala A, Kautiainen H, et al. Monocyte CD14 and soluble CD14 in 236. Boman J, Allard A, Persson K, et al. Rapid diagnosis of respiratory Chlamydia predicting mortality of patients with severe community acquired infection. pneumoniae infection by nested touchdown polymerase chain reaction compared Scand J Infect Dis 2007;39:596–603. with culture and antigen detection by EIA. J Infect Dis 1997;175:1523–6. 268. Christ-Crain M, Morgenthaler NG, Stolz D, et al. Pro-adrenomedullin to predict 237. Sillis M, Wreghitt TG, Paul ID, et al. Chlamydial respiratory infections. Don’t get severity and outcome in community-acquired pneumonia. Crit Care 2006;10:R96. bogged down by differentiating species. BMJ 1993;307:62–3. 269. Coelho L, Povoa P, Almeida E, et al. Usefulness of C-reactive protein in monitoring 238. Kutlin A, Tsumura N, Emre U, et al. Evaluation of Chlamydia immunoglobulin M the severe community-acquired pneumonia clinical course. Crit Care 2007;11(28). (IgM), IgG, and IgA rELISAs Medac for diagnosis of Chlamydia pneumoniae infection. 270. Kruger S, Papassotiriou J, Marre R, et al. Pro-atrial natriuretic peptide and pro- Clin Diagn Lab Immunol 1997;4:213–6. vasopressin to predict severity and prognosis in community-acquired pneumonia: 239. Ewig S, Ruiz M, Mensa J, et al. Severe community-acquired pneumonia. results from the German competence network CAPNETZ. Intensive Care Med Assessment of severity criteria. Am J Respir Crit Care Med 1998;158:1102–8. 2007;33:2069–78. on October 1, 2021 by guest. Protected copyright. 240. Meyer RJ, Town GI, Harre`E,et al. An audit of the assessment and management of 271. Prat C, Lacoma A, Dominguez J, et al. Midregional pro-atrial natriuretic peptide as a adults admitted to Christchurch Hospital with community acquired pneumonia. NZ prognostic marker in pneumonia. J Infect 2007;55:400–7. Med J 1997;110:349–52. 272. Brunkhorst FM, Al-Nawas B, Krummenauer F, et al. Procalcitonin, C-reactive 241. Neill AM, Martin IR, Weir R, et al. Community acquired pneumonia: aetiology and protein and APACHE II score for risk evaluation in patients with severe pneumonia. usefulness of severity criteria on admission. Thorax 1996;51:1010–6. Clin Microbiol Infect 2002;8:93–100. 242. Farr BM, Sloman AJ, Fisch MJ. Predicting death in patients hospitalized for 273. Shilon Y, Shitrit AB-G, Rudensky B, et al. A rapid quantitative D-dimer assay at community-acquired pneumonia. Ann Intern Med 1991;115:428–36. admission correlates with the severity of community acquired pneumonia. Blood 243. Fine MJ, Smith MA, Carson CA, et al. Prognosis and outcomes of patients with Coagul Fibrinolysis 2003;14:745–8. community-acquired pneumonia. A meta-analysis. JAMA 1996;275:134–41. 274. Querol-Ribelles JM, Tenias JM, Grau E, et al. Plasma D-dimer levels correlate 244. Fine MJ, Singer DE, Hanusa BH, et al. Validation of a pneumonia prognostic index with outcomes in patients with community-acquired pneumonia. Chest using the MedisGroups Comparative Hospital Database. Am J Med 1993;94:153–9. 2004;126:1087–92. 245. Hedlund J, Kalin M, Ortqvist A. Recurrence of pneumonia in middle-aged and 275. Tapson VF. Risk factors in community-acquired pneumonia: can they be quantified? elderly adults after hospital-treated pneumonia: aetiology and predisposing Eur Respir Rev 1998;8:291–4. conditions. Scand J Infect Dis 1997;29:387–92. 276. Niederman MS, Feldman C, Richards GA. Combining information from prognostic 246. Conte HA, Chen YT, Mehal W, et al. A prognostic rule for elderly patients admitted scoring tools for CAP: an American view on how to get the best of all worlds with community-acquired pneumonia. Am J Med 1999;106:20–8. [comment]. Eur Respir J 2006;27:9–11. 247. Kothe H, Bauer T, Marre R, et al. Outcome of community-acquired pneumonia: 277. Gleason PP, Kapoor WN, Stone RA, et al. Medical outcomes and antimicrobial influence of age, residence status and antimicrobial treatment. Eur Respir J costs with the use of the American Thoracic Society guidelines for outpatients with 2008;32:139–46. community-acquired pneumonia. JAMA 1997;278:32–9. 248. Fine MJ, Hanusa BH, Lave JR, et al. Comparison of a disease-specific and a generic 278. Marras TK, Chan CK. Use of guidelines in treating community-acquired pneumonia. severity of illness measure for patients with community-acquired pneumonia. J Gen Chest 1998;113:1689–94. Intern Med 1995;10:359–68. 279. Atlas SJ, Benzer TI, Borowsky LH, et al. Safely increasing the proportion of patients 249. Pachon J, Prados MD, Capote F, et al. Severe community-acquired pneumonia. with community-acquired pneumonia treated as outpatients: an interventional trial. Etiology, prognosis, and treatment. Am Rev Respir Dis 1990;142:369–73. Arch Intern Med 1998;158:1350–6. 250. Leroy O, Santre´C, Beuscart C, et al. A five-year study of severe community- 280. Yealy DM, Auble TE, Stone RA, et al. Effect of increasing the intensity of acquired pneumonia with emphasis on prognosis in patients admitted to an implementing pneumonia guidelines: a randomized, controlled trial. Ann Intern Med intensive care unit. Intensive Care Med 1995;21:24–31. 2005;143:881–94.

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii49 BTS guidelines

281. Renaud B, Coma E, Labarere J, et al. Routine use of the Pneumonia Severity Index 311. Scottish Intercollegiate Guideline Network. Prophylaxis of venous Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from for guiding the site-of-treatment decision of patients with pneumonia in the thromboembolism. 2002. http://www.sign.ac.uk/guidelines/fulltext/62/index.html. emergency department: a multicenter, prospective, observational, controlled cohort 312. Mismetti P, Laporte-Simitsidis S, Tardy B, et al. Prevention of venous study. Clin Infect Dis 2007;44:41–9. thromboembolism in internal medicine with unfractionated or low-molecular-weight 282. Richeldi L, De Guglielmo M, Fabbri LM, et al. Management of CAP using a validated heparins: a meta-analysis of randomised clinical trials. Thromb Haemost risk score. Thorax 2005;60:172–3. 2000;83:14–9. 283. Barlow G, Nathwani D, Williams F, et al. Reducing door-to-antibiotic time in 313. NHS Lothian. NHS Lothian Antithrombotic Guide. 2006. community-acquired pneumonia: controlled before-and-after evaluation and cost- 314. Mundy LM, Leet TL, Darst K, et al. Early mobilization of patients hospitalized with effectiveness analysis. Thorax 2007;62:67–74. community-acquired pneumonia. Chest 2003;124:883–9. 284. Tang CM, Macfarlane JT. Early management of younger adults dying of community 315. Tydeman DE. An investigation into the effectiveness of physiotherapy in the acquired pneumonia. Respir Med 1993;87:289–94. treatment of patients with community acquired pneumonia. Physio Pract 285. Gladman J, Barer D, Venkatesan P, et al. Outcome of pneumonia in the elderly: a 1989;5:75–8. hospital survey. Clin Rehab 1991;5:201–5. 316. Bjo¨rkqvistM, Wiberg B, Bodin L, et al. Bottle-blowing in hospital-treated patients 286. Capelastegui A, Espana PP, Quintana JM, et al. Validation of a predictive rule for with community-acquired pneumonia. Scand J Infect Dis 1997;29:77–82. the management of community-acquired pneumonia. Eur Respir J 2006;27:151–7. 317. National Institute for Health and Clinical Excellence (NICE). Acutely ill 287. Myint PK, Kamath AV, Vowler SL, et al. Severity assessment criteria recommended patients in hospital. Clinical Guideline 50. July 2007. by the British Thoracic Society (BTS) for community-acquired pneumonia (CAP) and 318. Menendez R, Cavalcanti M, Reyes S, et al. Markers of treatment failure in older patients. Should SOAR (systolic blood pressure, oxygenation, age and hospitalised community acquired pneumonia. Thorax 2008;63:447–52. respiratory rate) criteria be used in older people? A compilation study of two 319. Halm EA, Fine MJ, Kapoor WN, et al. Instability on hospital discharge and the risk prospective cohorts. Age Ageing 2006;35:286–91. of adverse outcomes in patients with pneumonia. Arch Intern Med 288. Aujesky D, Auble TE, Yealy DM, et al. Prospective comparison of three validated 2002;162:1278–84. prediction rules for prognosis in community-acquired pneumonia. Am J Med 320. Dagan E, Novack V, Porath A. Adverse outcomes in patients with community 2005;118:384–92. acquired pneumonia discharged with clinical instability from Internal Medicine 289. Barlow G, Nathwani D, Davey P. The CURB65 pneumonia severity score Department. Scand J Infect Dis 2006;38:860–6. outperforms generic sepsis and early warning scores in predicting mortality in 321. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and community-acquired pneumonia. Thorax 2007;62:253–9. guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus 290. Spindler C, Ortqvist A. Prognostic score systems and community-acquired Conference Committee. American College of Chest Physicians/Society of Critical bacteraemic pneumococcal pneumonia. Eur Respir J 2006;28:816–23. Care Medicine. Chest 1992;101:1644–55. 291. Buising KL, Thursky KA, Black JF, et al. A prospective comparison of severity 322. Demoule A, Girou E, Richard J-C, et al. Benefits and risks of success or failure of scores for identifying patients with severe community acquired pneumonia: noninvasive ventilation. Intensive Care Med 2006;32:1756–65. reconsidering what is meant by severe pneumonia. Thorax 2006;61:419–24. 323. Sinuff T, Cook DJ. Health technology assessment in the ICU: noninvasive positive 292. Shindo Y, Sato S, Maruyama E, et al. Comparison of severity scoring systems pressure ventilation for acute respiratory failure. J Crit Care 2003;18:59–67. A-DROP and CURB-65 for community-acquired pneumonia. Respirology 324. Keenan SP, Sinuff T, Cook DJ, et al. Does noninvasive positive pressure ventilation 2008;13:731–5. improve outcome in acute hypoxemic respiratory failure? A systematic review. Crit 293. Loh L-C. Community-acquired pneumonia in Malaysian patients: addition of Care Med 2004;32:2516–23. macrolide and the use of BTS ‘‘curb’’ index to assess severity. Med J Malaysia 325. Confalonieri M, Potena A, Carbone G, et al. Acute respiratory failure in patients 2006;61:128–30. with severe community-acquired pneumonia. A prospective randomized evaluation 294. Capelastegui A, Gorordo I, et al. Development and validation of a Espana PP, of noninvasive ventilation. Am J Respir Crit Care Med 1999;160:1585–91. clinical prediction rule for severe community-acquired pneumonia. Am J Respir Crit 326. Delclaux C, L’Her E, Alberti C, et al. Treatment of acute hypoxemic nonhypercapnic Care Med 2006;174:1249–56. respiratory insufficiency with continuous positive airway pressure delivered by a face 295. Ananda-Rajah MR, Charles PG, Melvani S, et al. Comparing the pneumonia mask: a randomized controlled trial. JAMA 2000;284:2352–60. severity index with CURB-65 in patients admitted with community acquired 327. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant pneumonia. Scand J Infect Dis 2008;40:293–300. human activated protein C for severe sepsis. N Engl J Med 2001;344:699–709. 296. Bauer TT, Ewig S, Marre R, et al. CRB-65 predicts death from community-acquired 328. Laterre P-F, Garber G, Levy H, et al. Severe community-acquired pneumonia as a pneumonia. J Intern Med 2006;260:93–101. cause of severe sepsis: data from the PROWESS study. Crit Care Med http://thorax.bmj.com/ 297. Schaaf B, Kruse J, Rupp J, et al. Sepsis severity predicts outcome in community- 2005;33:952–61. acquired pneumococcal pneumonia. Eur Respir J 2007;30:517–24. 329. Salanti G, Cardona AF. Human recombinant activated protein C 298. Man SY, Lee N, Ip M, et al. Prospective comparison of three predictive rules for Marti-Carvajal A, for severe sepsis. Cochrane Database Syst Rev 2008;(1):CD004388. assessing severity of community-acquired pneumonia in Hong Kong. Thorax 2007;62:348–53. 330. Confalonieri M, Urbino R, Potena A, et al. Hydrocortisone infusion for severe 299. Bont J, Hak E, Hoes AW, et al. A prediction rule for elderly primary-care patients community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit with lower respiratory tract infections. Eur Respir J 2007;29:969–75. Care Med 2005;171:242–8. 300. Myint PK, Kamath AV, Vowler SL, et al. Simple modification of CURB-65 better 331. Gorman SK, Slavik RS, Marin J. Corticosteroid treatment of severe community- identifies patients including the elderly with severe CAP. Thorax 2007;62:1015–6. acquired pneumonia. Ann Pharmacother 2007;41:1233–7. 301. Ewig S, de Roux A, Bauer T, et al. Validation of predictive rules and indices of 332. Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic severity for community acquired pneumonia. Thorax 2004;59:421–7. shock. N Engl J Med 2008;358:111–24. on October 1, 2021 by guest. Protected copyright. 302. Buising KL, Thursky KA, Black JF, et al. Identifying severe community-acquired 333. Cheng AC, Stephens DP, Currie BJ. Granulocyte-colony stimulating factor (G-CSF) pneumonia in the emergency department: a simple clinical prediction tool. Emerg as an adjunct to antibiotics in the treatment of pneumonia in adults. Cochrane Med Australas 2007;19:418–426. Database Syst Rev 2007;(2):CD004400. 303. Charles PG, Wolfe R, Whitby M, et al. SMART-COP: a tool for predicting the need 334. Leroy O, Guilley J, Georges H, et al. Effect of hospital-acquired ventilator-associated for intensive respiratory or vasopressor support in community-acquired pneumonia. pneumonia on mortality of severe community-acquired pneumonia. J Crit Care Clin Infect Dis 2008;47:375–84. 1999;14:12–9. 304. Leroy O, Devos P, Guery B, et al. Simplified prediction rule for prognosis of patients 335. Caine M, Lim WS, Macfarlane JT, et al. Keeping patients informed about their with severe community-acquired pneumonia in ICUs. Chest 1999;116:157–65. illness: community acquired pneumonia. Thorax 2000;55(Suppl 3):A71. 305. Farr BM, Woodhead MA, Macfarlane JT, et al. Risk factors for community-acquired 336. Impallomeni M, Galletly NP, Wort SJ, et al. Increased risk of diarrhoea caused by pneumonia diagnosed by general practitioners in the community. Respir Med Clostridium difficile in elderly patients receiving cefotaxime. BMJ 1995;311:1345–6. 2000;94:422–7. 337. Riley TV. Clostridium difficile: a pathogen of the nineties. Eur J Clin Microbiol Infect 306. Tydeman DE, Chandler AR, Graveling BM, et al. An investigation into the effects of Dis 1998;17:137–41. exercise tolerance training on patients with chronic airways obstruction. 338. Zadik PM, Moore AP. Antimicrobial associations of an outbreak of diarrhoea due to Physiotherapy 1984;70:261–4. Clostridium difficile. J Hosp Infect 1998;39:189–93. 307. LaCroix AZ, Lipson S, Miles TP, et al. Prospective study of pneumonia 339. MacGowan AP, Feeney R, Brown I, et al. Health care resource utilization and hospitalizations and mortality of U.S. older people: the role of chronic conditions, antimicrobial use in elderly patients with community-acquired lower respiratory tract health behaviors, and nutritional status. Public Health Rep 1989;104:350–60. infection who develop Clostridium difficile-associated diarrhoea. J Antimicrob 308. Levin KP, Hanusa BH, Rotondi A, et al. Arterial blood gas and pulse oximetry in Chemother 1997;39:537–41. initial management of patients with community-acquired pneumonia. J Gen Intern 340. Settle CD, Wilcox MH, Fawley WN, et al. Prospective study of the risk of Med 2001;16:590–8. Clostridium difficile diarrhoea in elderly patients following treatment with cefotaxime 309. Fulmer JD, Snider GL. American College of Chest Physicians/National Heart, Lung, or piperacillin-tazobactam. Aliment Pharmacol Ther 1998;12:1217–23. and Blood Institute National Conference on Oxygen Therapy. Heart Lung 341. Spencer RC. The role of antimicrobial agents in the aetiology of Clostridium difficile- 1984;13:550–62. associated disease. J Antimicrob Chemother 1998;41(Suppl C):21–7. 310. Marrie TJ, Lau CY, Wheeler SL, et al. A controlled trial of a critical pathway for 342. Ludlum H, Brown N, Sule O, et al. An antibiotic policy associated with reduced risk treatment of community-acquired pneumonia. CAPITAL Study Investigators. of Clostridium difficile-associated diarrhoea. Age Aging 1999;28:578–80. Community-Acquired Pneumonia Intervention Trial Assessing Levofloxacin. JAMA 343. Johnson AP. Antibiotic resistance among clinically important gram-positive 2000;283:749–55. bacteria in the UK. J Hosp Infect 1998;40:17–26. iii50 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

344. Felmingham D, Washington J. Trends in the antimicrobial susceptibility of bacterial 372. Van den Brande P, Vondra V, Vogel F, et al. Sequential therapy with cefuroxime Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from respiratory tract pathogens—findings of the Alexander Project 1992–1996. followed by cefuroxime axetil in community-acquired pneumonia. Chest J Chemother 1999;11(Suppl 1):5–21. 1997;112:406–15. 345. Pallares R, Linares J, Vadillo M, et al. Resistance to penicillin and cephalosporin 373. Vetter N, Stamler D, O’Neill S, et al. Clarithromycin vs combined cefuroxime and and mortality from severe pneumococcal pneumonia in Barcelona, Spain. erythromycin in the treatment of hospitalized community-acquired pneumonia N Engl J Med 1995;333:474–80. patients: intravenous followed by oral therapy. Clin Drug Invest 1997;14:439–49. 346. Einarsson S, Kristjansson M, Kristinsson KG, et al. Pneumonia caused by penicillin- 374. O’Doherty B, Muller O. Randomized, multicentre study of the efficacy and tolerance non-susceptible and penicillin-susceptible pneumococci in adults: a case-control of azithromycin versus clarithromycin in the treatment of adults with mildto study. Scand J Infect Dis 1998;30:253–6. moderate community-acquired pneumonia. Azithromycin Study Group. Eur J Clin 347. Klugman K, Feldman C. The clinical relevance of antibiotic resistance in the Microbiol Infect Dis 1998;17:828–33. management of pneumoccocal pneumonia. Infect Dis Clin Pract 1998;7:180–4. 375. Carbon C, Ariza H, Rabie WJ, et al. Comparative study of levofloxacin and 348. Pallares R, Viladrich PF, Linares J, et al. Impact of antibiotic resistance on amoxycillin/clavulanic acid in adults with mild-to-moderate community-acquired chemotherapy for pneumococcal infections. Microb Drug Resist 1998;4:339–47. pneumonia. Clin Microbiol Infect 1999;5:724–32. 349. Garau J, Aguilar L, Rodriguez-Creixems M, et al. Influence of comorbidity and 376. Rovira E, Martinez-Moragon E, Belda A, et al. Treatment of community-acquired severity on the clinical outcome of bacteremic pneumococcal pneumonia treated pneumonia in outpatients: randomized study of clarithromycin alone versus with beta-lactam monotherapy. J Chemother 1999;11:266–72. clarithromycin and cefuroxime. Respiration 1999;66:413–8. 350. Ewig S, Kleinfeld T, Bauer T, et al. Comparative validation of prognostic rules for 377. Johnson RH, Levine S, Traub SL. Sequential intravenous/oral ciprofloxacin community-acquired pneumonia in an elderly population. Eur Respir J compared with parenteral ceftrixone in the treatment of hospitalized patients with 1999; :370–5. 14 community-acquired pneumonia. Infect Dis Clin Pract 1996;5:265–72. 351. Farrell DJ, Felmingham D, Shackcloth J, et al. Non-susceptibility trends and 378. Bartoloni A, Strohmeyer M, Corti G, et al. Multicenter randomized trial comparing serotype distributions among Streptococcus pneumoniae from community-acquired meropenem (1.5 g daily) and imipenem/cilastatin (2 g daily) in the hospital respiratory tract infections and from bacteraemias in the UK and Ireland, 1999 to treatment of community-acquired pneumonia. Drugs Exp Clin Res 1999;25:243–52. 2007. J Antimicrob Chemother 2008;62(Suppl 2):ii87–95. 379. Garau J, Twynholm M, Garcia-Mendez E, et al. Oral pharmacokinetically enhanced 352. Chen DK, McGeer A, de Azavedo JC, et al. Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. Canadian Bacterial co-amoxiclav 2000/125 mg, twice daily, compared with co-amoxiclav 875/125 mg, Surveillance Network. N Engl J Med 1999;341:233–9. three times daily, in the treatment of community-acquired pneumonia in European 353. Powell M, Yeo SF, Seymour A, et al. Antimicrobial resistance in Haemophilus adults. J Antimicrob Chemother 2003;52:826–36. influenzae from England and Scotland in 1991. J Antimicrob Chemother 380. Siquier B, Sanchez-Alvarez J, Garcia-Mendez E, et al. Efficacy and safety of twice- 1992;29:547–54. daily pharmacokinetically enhanced amoxicillin/clavulanate (2000/125 mg) in the 354. Morrissey I, Maher K, Williams L, et al. Non-susceptibility trends among treatment of adults with community-acquired pneumonia in a country with a high Haemophilus influenzae and Moraxella catarrhalis from community-acquired prevalence of penicillin-resistant Streptococcus pneumoniae. J Antimicrob respiratory tract infections in the UK and Ireland, 1999–2007. J Antimicrob Chemother 2006;57:536–45. Chemother 2008;62(Suppl 2):ii97–103. 381. Dunbar LM. Current issues in the management of bacterial respiratory tract 355. Andrews J, Ashby J, Jevons G, et al. A comparison of antimicrobial resistance disease: the challenge of antibacterial resistance. Am J Med Sci 2003;326:360–8. rates in Gram-positive pathogens isolated in the UK from October 1996 to January 382. Baumgartner JD, Glauser MP. Tolerance study of ceftriaxone compared with 1997 and October 1997 to January 1998. J Antimicrob Chemother 2000;45:285–93. amoxicillin in patients with pneumonia. Am J Med 1984;77:54–8. 356. Nielsen K, Bangsborg JM, Hoiby N. Susceptibility of Legionella species to five 383. Fredlund H, Bodin L, Back E, et al. Antibiotic therapy in pneumonia: a comparative antibiotics and development of resistance by exposure to erythromycin, study of parenteral and oral administration of penicillin. Scand J Infect Dis ciprofloxacin, and rifampicin. Diagn Microbiol Infect Dis 2000;36:43–8. 1987;19:459–66. 357. Lode H, Garau J, Grassi C, et al. Treatment of community-acquired pneumonia: a 384. Zuck P, Rio Y, Ichou F. Efficacy and tolerance of cefpodoxime proxetil compared randomized comparison of sparfloxacin, amoxycillin-clavulanic acid and with ceftriaxone in vulnerable patients with bronchopneumonia. J Antimicrob erythromycin. Eur Respir J 1995;8:1999–2007. Chemother 1990;26(Suppl E):71–7. 358. Soman A, Honeybourne D, Andrews J, et al. Concentrations of moxifloxacin in 385. Poirier R. Comparative study of clarithromycin and roxithromycin in the treatment of serum and pulmonary compartments following a single 400 mg oral dose in patients community-acquired pneumonia. J Antimicrob Chemother 1991;27(Suppl A):109–16. undergoing fibre-optic bronchoscopy. J Antimicrob Chemother 1999;44:835–8.

386. Koulla-Shiro S, Kuaban C, Auckenthaler R, et al. Adult response to initial treatment http://thorax.bmj.com/ 359. Hoffken G, Meyer HP, Winter J, et al. The efficacy and safety of two oral with ampicillin in community acquired pneumonia in Yaounde, Cameroon. Cent moxifloxacin regimens compared to oral clarithromycin in the treatment of Afr J Med 1993;39:188–92. community-acquired pneumonia. Respir Med 2001;95:553–64. 387. Gaillat J, Bru JP, Sedallian A. Penicillin G/ofloxacin versus erythromycin/amoxicillin- 360. Petitpretz P, Arvis P, Marel M, et al. Oral moxifloxacin vs high-dosage amoxicillin in clavulanate in the treatment of severe community-acquired pneumonia. Eur J Clin the treatment of mild-to-moderate, community-acquired, suspected pneumococcal Microbiol Infect Dis 1994;13:639–44. pneumonia in adults. Chest 2001;119:185–95. 388. Low DE, Mandell LA. A prospective open-label multi-centre trial on the use of 1 g, 361. Fogarty C, Grossman C, Williams J, et al. Efficacy and safety of moxifloxacin vs. once daily ceftriaxone in lower respiratory tract infections. Can J Infect Dis clarithromycin for community-acquired pneumonia. Infect Med 1999:748–63. 1994;5(Suppl C):3–8C. 362. Torres A, Muir JF, Corris P, et al. Effectiveness of oral moxifloxacin in standard first- 389. Uzun O, Hayran M, Akova M, et al. Efficacy of a three-day course of azithromycin in line therapy in community-acquired pneumonia. Eur Respir J 2003;21:135–43.

the treatment of community-acquired pneumococcal pneumonia. Preliminary report. on October 1, 2021 by guest. Protected copyright. 363. Anon. Britsh National Formulary. London: BMJ Publishing Group and RPS Publishing, J Chemother 1994;6:53–7. 2008. 390. Jang TN, Liu CY, Wang FD, et al. A randomized comparative study on the safety 364. Anderson G, Esmonde TS, Coles S, et al. A comparative safety and efficacy study and efficacy of clarithromycin and erythromycin in treating community-acquired of clarithromycin and erythromycin stearate in community-acquired pneumonia. pneumonia. Zhonghua Yi Xue Za Zhi (Taipei) 1995;55:302–6. J Antimicrob Chemother 1991;27(Suppl A):117–24. 391. Rizzato G, Montemurro L, Fraioli P, et al. Efficacy of a three day course of 365. Chien SM, Pichotta P, Siepman N, et al. Treatment of community-acquired azithromycin in moderately severe community-acquired pneumonia. Eur Respir J pneumonia. A multicenter, double-blind, randomized study comparing clarithromycin 1995;8:398–402. with erythromycin. Canada-Sweden Clarithromycin-Pneumonia Study Group. Chest 392. Oh HM, Ng AW, Lee SK. Cefuroxime compared to amoxicillin-clavulanic acid in the 1993;103:697–701. treatment of community-acquired pneumonia. Singapore Med J 1996;37:255–7. 366. Green JA, Butler T, Todd WM. Randomized double-blind trial of the comparative efficacy and safety of cefpodoxime proxetil and cefaclor in the treatment of acute 393. Siegel RE, Halpern NA, Almenoff PL, et al. A prospective randomized study of community-acquired pneumonia. Curr Ther Res 1994;55:1003–15. inpatient IV antibiotics for community-acquired pneumonia. The optimal duration of 367. Rizzato G, Allegra L. Efficacy and tolerability of a teicoplanin-ciprofloxacin therapy. Chest 1996;110:965–71. combination in severe community-acquired pneumonia. Clin Drug Invest 394. Genne D, Siegrist HH, Humair L, et al. Clarithromycin versus amoxicillin-clavulanic 1997;14:337–45. acid in the treatment of community-acquired pneumonia. Eur J Clin Microbiol Infect 368. Bohte R, van’t Wout JW, Lobatto S, et al. Efficacy and safety of azithromycin Dis 1997;16:783–8. versus benzylpenicillin or erythromycin in community-acquired pneumonia. Eur J Clin 395. Ho A, Leung R, Lai CK, et al. Hospitalized patients with community-acquired Microbiol Infect Dis 1995;14:182–7. pneumonia in Hong Kong: a randomized study comparing imipenem/cilastatin and 369. Chan R, Hemeryck L, O’Regan M, et al. Oral versus intravenous antibiotics for ceftazidime. Respiration 1997;64:224–8. community acquired lower respiratory tract infection in a general hospital: open, 396. Cabellos C, Ariza J, Barreiro B, et al. Current usefulness of procaine penicillin in the randomised controlled trial. BMJ 1995;310:1360–2. treatment of pneumococcal pneumonia. Eur J Clin Microbiol Infect Dis 370. Plouffe JF, Herbert MT, File TM Jr, et al. Ofloxacin versus standard therapy in 1998;17:265–8. treatment of community-acquired pneumonia requiring hospitalization. Pneumonia 397. Fogarty CM, Sullivan JG, Chattman MS, et al. Once a day levofloxacin in the Study Group. Antimicrob Agents Chemother 1996;40:1175–9. treatment of mild to moderate and severe community-acquired pneumonia in adults. 371. File TM Jr, Segreti J, Dunbar L, et al. A multicenter, randomized study comparing Infect Dis Clin Pract 1998;7:400–7. the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone 398. Rhew DC, Hackner D, Henderson L, et al. The clinical benefit of in-hospital and/or cefuroxime axetil in treatment of adults with community-acquired observation in ‘low-risk’ pneumonia patients after conversion from parenteral to oral pneumonia. Antimicrob Agents Chemother 1997;41:1965–72. antimicrobial therapy. Chest 1998;113:142–6.

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii51 BTS guidelines

399. Speich R, Imhof E, Vogt M, et al. Efficacy, safety, and tolerance of piperacillin/ 427. Ragnar NS. Atypical pneumonia in the Nordic countries: aetiology and clinical Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from tazobactam compared to co-amoxiclav plus an aminoglycoside in the treatment of results of a trial comparing fleroxacin and doxycycline. Nordic Atypical Pneumonia severe pneumonia. Eur J Clin Microbiol Infect Dis 1998;17:313–7. Study Group. J Antimicrob Chemother 1997;39:499–508. 400. Shorr AF, Khashab MM, Xiang JX, et al. Levofloxacin 750-mg for 5 days for the 428. O’Doherty B, Dutchman DA, Pettit R, et al. Randomized, double-blind, comparative treatment of hospitalized Fine risk class III/IV community-acquired pneumonia study of grepafloxacin and amoxycillin in the treatment of patients with community- patients. Respir Med 2006;100:2129–36. acquired pneumonia. J Antimicrob Chemother 1997;40(Suppl A):73–81. 401. File TM Jr. Community-associated methicillin-resistant Staphylococcus aureas: not 429. Aubier M, Verster R, Regamey C, et al. Once-daily sparfloxacin versus high-dosage only a cause of skin infections, also a new cause of pneumonia. Curr Opin Infect Dis amoxicillin in the treatment of community-acquired, suspected pneumococcal 2005;18:123–4. pneumonia in adults. Sparfloxacin European Study Group. Clin Infect Dis 402. Fogarty C, Siami G, Kohler R, et al. Multicenter, open-label, randomized study to 1998;26:1312–20. compare the safety and efficacy of levofloxacin versus ceftriaxone sodiumand 430. Salvarezza CR, Mingrone H, Fachinelli H, et al. Comparison of roxithromycin with erythromycin followed by clarithromycin and amoxicillin-clavulanate in the treatment cefixime in the treatment of adults with community-acquired pneumonia. of serious community-acquired pneumonia in adults. Clin Infect Dis 2004;38(Suppl J Antimicrob Chemother 1998;41(Suppl B):75–80. 1):S16–23. 431. Tremolieres F, de Kock F, Pluck N, et al. Trovafloxacin versus high-dose amoxicillin 403. Plouffe JF, Breiman RF, Fields BS, et al. Azithromycin in the treatment of Legionella (1 g three times daily) in the treatment of community-acquired bacterial pneumonia. pneumonia requiring hospitalization. Clin Infect Dis 2003;37:1475–80. Eur J Clin Microbiol Infect Dis 1998;17:447–53. 404. Welte T, Petermann W, Schurmann D, et al. Treatment with sequential intravenous 432. Zervos M, Nelson M. Cefepime versus ceftriaxone for empiric treatment of or oral moxifloxacin was associated with faster clinical improvement than was hospitalized patients with community-acquired pneumonia. The Cefepime Study standard therapy for hospitalized patients with community-acquired pneumonia who Group. Antimicrob Agents Chemother 1998;42:729–33. received initial parenteral therapy. Clin Infect Dis 2005;41:1697–705. 433. Daniel R. Trovafloxacin vs high dose amoxicillin in the treatment of community- 405. Lode H, Grossman C, Choudhri S, et al. Sequential IV/PO moxifloxacin treatment acquired bacterial pneumonia. Drugs 1999;58(Suppl 2):304–5. of patients with severe community-acquired pneumonia. Respir Med 434. Daniel R. Oral trovafloxacin compared with amoxicillin (plus optional erythromycin) 2003;97:1134–42. for the treatment of mild to moderate community-acquired pneumonia. Drugs 406. Wallace RJ Jr, Martin RR, Quinones FJ, et al. Ceforanide and cefazolin therapy 1999;58(Suppl 2):320–2. of pneumonia: comparative clinical trial. Antimicrob Agents Chemother 435. Grossman RF, Campbell DA, Landis SJ, et al. Treatment of community-acquired 1981;20:648–52. pneumonia in the elderly: the role of cefepime, a fourth-generation cephalosporin. 407. Grieco MM, Lange M, Daniels JA, et al. Single-blind controlled study of ceftizoxime J Antimicrob Chemother 1999;43:549–54. and cefamandole in the treatment of community-acquired pneumonia. J Antimicrob 436. Moola S, Hagberg L, Churchyard GA, et al. A multicenter study of grepafloxacin and Chemother 1982;10(Suppl C):223–5. clarithromycin in the treatment of patients with community-acquired pneumonia. 408. Wallace RJ Jr, Niefield SL, Waters S, et al. Comparative trial of cefonicid and Chest 1999;116:974–83. ¡ cefamandole in the therapy of community-acquired pneumonia. Antimicrob Agents 437. Peterson J. Oral trovafloxacin vs oral cefuroxime erythromycin in community Chemother 1982;21:231–5. acquired pneumonia. Drugs 1999;58(Suppl 2):301–3. 409. Keeton GR, Kehoe B, Phillips SW, et al. Ceftazidime and cefamandole in the 438. Ramirez J, Unowsky J, Talbot GH, et al. Sparfloxacin versus clarithromycin in the treatment of pneumonia. J Antimicrob Chemother 1983;12(Suppl A):27–30. treatment of community-acquired pneumonia. Clin Ther 1999;21:103–17. 410. Geckler RW, McCormack GD, Goodman JS. Comparison of cefonicid and 439. Leophonte P, File T, Feldman C. Gemifloxacin once daily for 7 days compared to cefamandole for the treatment of community-acquired infections of the lower amoxicillin/clavulanic acid thrice daily for 10 days for the treatment of respiratory tract. Rev Infect Dis 1984;6(Suppl 4):S847–52. community-acquired pneumonia of suspected pneumococcal origin. Respir Med 2004;98:708–20. 411. Weber DJ, Calderwood SB, Karchmer AW, et al. Ampicillin versus cefamandole as 440. Tellier G, Niederman MS, Nusrat R, et al. Clinical and bacteriological efficacy and initial therapy for community-acquired pneumonia. Antimicrob Agents Chemother safety of 5 and 7 day regimens of telithromycin once daily compared with a 10 day 1987;31:876–82. regimen of clarithromycin twice daily in patients with mild to moderate community- 412. Carbon C, Leophonte P, Petitpretz P, et al. Efficacy and safety of temafloxacin acquired pneumonia. J Antimicrob Chemother 2004;54:515–23. versus those of amoxicillin in hospitalized adults with community-acquired 441. Drehobl MA, De Salvo MC, Lewis DE, et al. Single-dose azithromycin microspheres pneumonia. Antimicrob Agents Chemother 1992;36:833–9. vs clarithromycin extended release for the treatment of mild-to-moderate 413. Kissling M. Cefetamet pivoxil in community-acquired pneumonia: an overview. Curr community-acquired pneumonia in adults. Chest 2005;128:2230–7. Med Res Opin 1992;12:631–9. http://thorax.bmj.com/ 442. Blaser MJ, Klaus BD, Jacobson JA, et al. Comparison of cefadroxil and cephalexin 414. Wiesner B, Wilen-Rosenqvist G, Lehtonen L. Twice daily dosing of erythromycin in the treatment of community-acquired pneumonia. Antimicrob Agents Chemother acistrate in the treatment of acute bronchitis and pneumonia. Arzneimittelforschung 1983;24:163–7. 1993;43:1014–7. 443. Cassell GH, Drnec J, Waites KB, et al. Efficacy of clarithromycin against 415. Aquino R, Lansang MA, Salvador A, et al. The effectiveness and safety of Mycoplasma pneumoniae. J Antimicrob Chemother 1991;27(Suppl A):47–59. ceftriaxone to cefetamet pivoxil vs ceftazidime to cefetamet pivoxil vs cefoperazone 444. Morales JO, Snead H. Efficacy and safety of intravenous cefotaxime for treating to cefetamet pivoxil in the treatment of community-acquired pneumonia in adult pneumonia in outpatients. Am J Med 1994;97:28–33. Filipinos. Phil J Intern Med 1994;31:237–40. 445. Ramirez JA. Switch therapy in community-acquired pneumonia. Diagn Microbiol 416. Liippo K, Tala E, Puolijoki H, et al. A comparative study of dirithromycin and Infect Dis 1995;22:219–23. erythromycin in bacterial pneumonia. J Infect 1994;28:131–9. 446. Higuera F, Hidalgo H, Feris J, et al. Comparison of oral cefuroxime axetil and oral 417. Williams D, Perri M, Zervos MJ. Randomized comparative trial with ampicillin/ amoxycillin/clavulanate in the treatment of community-acquired pneumonia. on October 1, 2021 by guest. Protected copyright. sulbactam versus cefamandole in the therapy of community acquired pneumonia. J Antimicrob Chemother 1996;37:555–64. Eur J Clin Microbiol Infect Dis 1994;13:293–8. 447. Berman SJ, Sieger B, Geckler W, et al. A comparative study of meropenem and 418. De Palma M, Rocchi D, Canepa G, et al. Single daily dose of cefodizime in patients ceftazidime in the treatment of patients hospitalized with community-acquired with community-acquired pneumonia: an open-label, controlled, randomized study. pneumonia. Curr Ther Res 1997;58:903–16. Clin Ther 1995;17:413–24. 448. Ailani RK, Agastya G, Mukunda BN, et al. Doxycycline is a cost-effective therapy 419. Hopkins S, Williams D. Five-day azithromycin in the treatment of patients with for hospitalized patients with community-acquired pneumonia. Arch Intern Med community-acquired pneumonia. Curr Ther Res 1995;56:915–25. 1999;159:266–70. 420. Aubier M, Lode H, Gialdroni-Grassi G, et al. Sparfloxacin for the treatment of 449. Schonwald S, Kuzman I, Oreskovic K, et al. Azithromycin: single 1.5 g dose in the community-acquired pneumonia: a pooled data analysis of two studies. J Antimicrob treatment of patients with atypical pneumonia syndrome—a randomized study. Chemother 1996;37(Suppl A):73–82. Infection 1999;27:198–202. 421. Hernandez JM, Sides GD, Conforti PM, et al. Clinical efficacy of dirithromycin in 450. Sherer Y, Bakshi E, Rotman P, et al. Comparative clinical study of cefonicid, patients with bacteremic pneumonia. Clin Ther 1996;18:1128–38. chloramphenicol, and penicillin in community-acquired pneumonia. Int J Mol Med 422. Ortqvist A, Valtonen M, Cars O, et al. Oral empiric treatment of community- 1998;2:343–8. acquired pneumonia. A multicenter, double-blind, randomized study comparing 451. Stocks JM, Wallace RJ Jr, Griffith DE, et al. Ofloxacin in community-acquired lower sparfloxacin with roxithromycin. The Scandinavian Sparfloxacin Study Group. Chest respiratory infections. A comparison with amoxicillin or erythromycin. Am J Med 1996;110:1499–506. 1989;87(6C):52–6S. 423. Portier H, May T, Proust A. Comparative efficacy of sparfloxacin in comparison with 452. Morandini G, Perduca M, Zannini G, et al. Clinical efficacy of azithromycin in lower amoxycillin plus ofloxacin in the treatment of community-acquired pneumonia. respiratory tract infections. J Chemother 1993;5:32–6. French Study Group. J Antimicrob Chemother 1996;37(Suppl A):83–91. 453. Finch RG, Woodhead MA. Practical considerations and guidelines for the 424. Rubinstein E. Safety profile of sparfloxacin in the treatment of respiratory tract management of community-acquired pneumonia. Drugs 1998;55:31–45. infections. J Antimicrob Chemother 1996;37(Suppl A):145–60. 454. Moreno S, Garcia-Leoni ME, Cercenado E, et al. Infections caused by erythromycin- 425. Donowitz GR, Brandon ML, Salisbury JP, et al. Sparfloxacin versus cefaclor in the resistant Streptococcus pneumoniae: incidence, risk factors, and response to treatment of patients with community-acquired pneumonia: a randomized, double- therapy in a prospective study. Clin Infect Dis 1995;20:1195–200. masked, comparative, multicenter study. Clin Ther 1997;19:936–53. 455. Jackson MA, Burry VF, Olson LC, et al. Breakthrough sepsis in macrolide-resistant 426. Drehobl M, Bianchi P, Keyserling CH, et al. Comparison of cefdinir and cefaclor in pneumococcal infection. Pediatr Infect Dis J 1996;15:1049–51. treatment of community-acquired pneumonia. Antimicrob Agents Chemother 456. Amsden GW. Pneumococcal macrolide resistance—myth or reality? J Antimicrob 1997;41:1579–83. Chemother 1999;44:1–6. iii52 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

457. Perez-Trallero E. Pneumococcal macrolide resistance—not a myth. J Antimicrob 479. el Moussaoui R, de Borgie CAJM, van den Broek P, et al. Effectiveness of Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from Chemother 2000;45:401–3. discontinuing antibiotic treatment after three days versus eight days in mild to 458. Carbon C, Poole MD. The role of newer macrolides in the treatment of community- moderate-severe community acquired pneumonia: randomised, double blind study. acquired respiratory tract infection. A review of experimental and clinical data. BMJ 2006;332:1355. J Chemother 1999;11:107–18. 480. Pedro-Botet L, Yu VL. Legionella: macrolides or quinolones? Clin Microbiol Infect 459. Moss PJ, Finch RG. The next generation: fluoroquinolones in the management of 2006;12(Suppl 3):25–30. acute lower respiratory infection in adults. Thorax 2000;55:83–5. 481. Sabria M, Pedro-Botet ML, Gomez J, et al. Fluoroquinolones vs macrolides in the 460. Robenshtok E, Shefet D, Gaafter-Gvili A, et al. Empiric antibiotic coverage of treatment of Legionnaires disease. Chest 2005;128:1401–5. atypical pathogens for community acquired pneumonia in hospitalized adults. 482. Blazquez Garrido RM, Espinosa Parra FJ, Alemany Frances L, et al. Antimicrobial Cochrane Database Systemat Rev 2008;(1):CD004418. chemotherapy for Legionnaires disease: levofloxacin versus macrolides. Clin Infect 461. Shefet D, Robenshtok E, Paul M, et al. Empirical atypical coverage for inpatients Dis 2005;40:800–6. with community-acquired pneumonia: systematic review of randomized controlled 483. Mykietiuk A, Carratala J, Fernandez-Sabe N, et al. Clinical outcomes for trials. Arch Intern Med 2005;165:1992–2000. hospitalized patients with Legionella pneumonia in the antigenuria era: the influence 462. Mills GD, Oehley MR, Arrol B. Effectiveness of beta lactam antibiotics compared of levofloxacin therapy. Clin Infect Dis 2005;40:794–9. with antibiotics active against atypical pathogens in non-severe community acquired 484. Owens RC Jr, Nolin TD. Antimicrobial-associated QT interval prolongation: points of pneumonia: meta-analysis. BMJ 2005;330:456. interest. Clin Infect Dis 2006;43:1603–11. 463. Sportel JH, Koeter GH, van Altena R, et al. Relation between beta-lactamase 485. Grau S, Antonio JM, Ribes E, et al. Impact of rifampicin addition to clarithromycin in producing bacteria and patient characteristics in chronic obstructive pulmonary Legionella pneumophila pneumonia. Int J Antimicrob Agents 2006;28:249–52. disease (COPD). Thorax 1995;50:249–53. 486. Hubbard RB, Mathur RM, MacFarlane JT. Severe community-acquired legionella 464. Meehan TP, Fine MJ, Krumholz HM, et al. Quality of care, process, and outcomes pneumonia: treatment, complications and outcome. Q J Med 1993;86:327–32. in elderly patients with pneumonia. JAMA 1997;278:2080–4. 487. Kirby J, Polis G, Romansky MJ. A controlled blind study of pneumococcal 465. Houck PM, Bratzler DW, Nsa W, et al. Timing of antibiotic administration and pneumonia treated with tetracycline and tetracycline plus 6-methyl prednisolone. outcomes for Medicare patients hospitalized with community-acquired pneumonia. Antibiot Ann 1959;7:175–81. Arch Intern Med 2004;164:637–44. 488. Roson B, Carratala J, Fernandez-Sabe N, et al. Causes and factors associated with 466. Simpson JC, Macfarlane JT, Watson J, et al. A national confidential enquiry into early failure in hospitalized patients with community-acquired pneumonia. Arch community acquired pneumonia deaths in young adults in England and Wales. Intern Med 2004;164:502–8. British Thoracic Society Research Committee and Public Health Laboratory Service. 489. Genne D, Sommer R, Kaiser L, et al. Analysis of factors that contribute to treatment Thorax 2000;55:1040–5. failure in patients with community-acquired pneumonia. Eur J Clin Microbiol Infect 467. Marston BJ, Plouffe JF, File TM Jr, et al. Incidence of community-acquired Dis 2006;25:159–66. pneumonia requiring hospitalization. Results of a population-based active 490. Menendez R, Torres A, Zalacain R, et al. Risk factors of treatment failure in community surveillance Study in Ohio. The Community-Based Pneumonia Incidence Study acquired pneumonia: implications for disease outcome. Thorax 2004;59:960–5. Group. Arch Intern Med 1997;157:1709–18. 491. Heffner JE, McDonald J, Barbieri C, et al. Management of parapneumonic 468. Houck PM, Bratzler DW, Nsa W, et al. Antibiotic administration in community- effusions. An analysis of physician practice patterns. Arch Surg 1995;130:433–8. acquired pneumonia. Chest 2004;126:320–1. 492. Light RW. A new classification of parapneumonic effusions and empyema. Chest 469. Metersky ML, Sweeney TA, Getzow MB, et al. Antibiotic timing and diagnostic 1995;108:299–301. uncertainty in Medicare patients with pneumonia: is it reasonable to expect all 493. Heffner JE, Brown LK, Barbieri C, et al. Pleural fluid chemical analysis in patients to receive antibiotics within 4 hours? Chest 2006;130:16–21. parapneumonic effusions. A meta-analysis. Am J Respir Crit Care Med 470. Welker JA, Huston M, McCue JD. Antibiotic timing and errors in diagnosing 1995;151:1700–8. pneumonia. Arch Intern Med 2008;168:351–6. 494. Ahmed RA, Marrie TJ, Huang JQ. Thoracic empyema in patients with community- 471. Kanwar M, Brar N, Khatib R, et al. Misdiagnosis of community-acquired pneumonia acquired pneumonia. Am J Med 2006;119:877–83. and inappropriate utilization of antibiotics: side effects of the 4-h antibiotic 495. Finley C, Clifton J, Fitzgerald JM, et al. Empyema: an increasing concern in Canada. administration rule. Chest 2007;131:1865–9. Can Respir J 2008;15:85–9. 472. Schulin T, Wennersten CB, Ferraro MJ, et al. Susceptibilities of Legionella spp. to 496. Farjah F, Symons RG, Krishnadasan B, et al. Management of pleural space infections: newer antimicrobials in vitro. Antimicrob Agents Chemother 1998;42:1520–3. a population-based analysis. J Thorac Cardiovasc Surg 2007;133:346–51.

473. Gleason PP, Meehan TP, Fine JM, et al. Associations between initial antimicrobial 497. Davies CW, Gleeson FV, Davies RJ. BTS guidelines for the management of pleural http://thorax.bmj.com/ therapy and medical outcomes for hospitalized elderly patients with pneumonia. infection. Thorax 2003;58(Suppl 2):ii18–28. Arch Intern Med 1999;159:2562–72. 498. Almirall J, Bolibar I, Serra-Prat M, et al. New evidence of risk factors for 474. Burgess DS, Lewis JS 2nd. Effect of macrolides as part of initial empiric therapy on community-acquired pneumonia: a population-based study. Eur Respir J medical outcomes for hospitalized patients with community-acquired pneumonia. 2008;31:1274–84. Clin Ther 2000;22:872–8. 499. Baik I, Curhan GC, Rimm EB, et al. A prospective study of age and lifestyle factors 475. MacGregor RR, Graziani AL. Oral administration of antibiotics: a rational alternative in relation to community-acquired pneumonia in US men and women. Arch Intern to the parenteral route. Clin Infect Dis 1997;24:457–67. Med 2000;160:3082–8. 476. Mandell LA, Bergeron MG, Gribble MJ, et al. Sequential antibiotic therapy: 500. Nuorti JP, Butler JC, Farley MM, et al. Cigarette smoking and invasive effective cost management and patient care. Can J Infect Dis 1995;6:306–15. pneumococcal disease. Active Bacterial Core Surveillance Team. N Engl J Med 477. Siegel RE, Alicea M, Lee A, et al. Comparison of 7 versus 10 days of antibiotic therapy 2000;342:681–9. for hospitalized patients with uncomplicated community-acquired pneumonia: a 501. West R, McNeill A, Raw M. Smoking cessation guidelines for health professionals: on October 1, 2021 by guest. Protected copyright. prospective, randomized, double-blind study. Am J Ther 1999;6:217–22. an update. Health Education Authority. Thorax 2000;55:987–99. 478. Nathwani D. Sequential switch therapy for lower respiratory tract infections: a 502. Berntsson E, Blomberg J, Lagergard T, et al. Etiology of community-acquired European perspective. Chest 1998;113(3 Suppl):211–8S. pneumonia in patients requiring hospitalization. Eur J Clin Microbiol 1985;4:268–72.

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii53 BTS guidelines

APPENDIX 1 CHECKLIST USED BY REVIEWERS FOR APPENDIX 2 ADDITIONAL CHECKLIST USED FOR APPRAISING Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from APPRAISING STUDIES STUDIES TO INFORM PNEUMONIA AETIOLOGY Study: ______Reviewer: ______Absolute requirements: Please complete section 1 first. If study OK, complete one of sections 2a–d as c Is this an original report? appropriate. c Were patients with CAP separately identified? c Was the study designed to assess CAP aetiology? 1. General: is the study relevant to our question? c Was the patient sample representative (eg, sufficient numbers, consecutive % Were the patients studied similar (in age, gender, disease severity …) to target cases, exclusions clearly defined)? patients? c Was the study of sufficient duration to exclude seasonal bias? % Were the outcome measures of interest to us and our patients? Data qualification: % Was the clinical setting (primary care, intensive care …) similar to our setting? c Is the geographical area clear and relevant? % Was the study carried out in a healthcare system similar to ours? c Is the patient age group defined? % Is the study design recognisable and appropriate, with clear methods described? c Are microbial investigations clearly defined? % Is the study recent enough to take account of any important advances? c Was the investigation biased towards a specific pathogen? % If negative, was this study large enough to provide useful information? c Is the setting community, hospital, intensive care or a combination?

2a. Studies of cause and effect (randomised trial of treatment) % Was assignment of patients to treatment truly randomised? % Was the planned therapy concealed from those recruiting patients before enrolment? % Were all patients who entered the study accounted for? % Were patients analysed in the groups to which they were initially randomised? % Were patients and doctors blind to the therapy given? % Were groups treated the same way, apart from the therapy? % Were the groups similar at the start of the trial?

2b. Studies of aetiology (case-control study of a harmful agent) % Were there two groups of cases, similar except for exposure to harmful agent? % Was occurrence of the outcome measured in the same way for both groups? % Were enough patients followed up for long enough for the outcome to develop? % Did exposure clearly precede the outcome? % Was there a dose-response gradient? % Was there a re-challenge, or improvement after the drug stopped? % Does the association make biological sense?

2c. Studies of diagnosis (evaluation of clinical findings or tests) % Was the finding or result compared with a 24 carat gold standard for diagnosis? % Was the finding or result determined blind to the gold standard? % Was the gold standard determined blind to the finding or test result?

% Was the gold standard determined in all cases, not just those with an abnormal http://thorax.bmj.com/ result?

2d. Studies of prognosis, prognostic index (cohort studies) % Was a defined sample of patients assembled at an early stage of the disease? % Were patients followed up long enough for the outcome to develop? % Was the outcome clearly defined, objective and assessed blind to exposure in all cases? % Was the performance of any prognostic index tested on a fresh set of cases? on October 1, 2021 by guest. Protected copyright.

3. Comments

iii54 Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 BTS guidelines

Appendix 3 Types of study and levels of evidence used to illuminate specific clinical questions Thorax: first published as 10.1136/thx.2009.121434 on 24 September 2009. Downloaded from Type of clinical question Evidence level Brief definition Types of study providing this level of evidence

Treatment Ia A good recent systematic review Systematic review of randomised trials Ib A rigorous study designed to answer the question A rigorous randomised trial comparing T with best alternative Is therapy T effective? II One or more prospective clinical studies A cohort study or faulty randomised trial III One or more retrospective clinical studies A case-control study IVa Formal expert consensus Delphi study of expert practice IVb Other information Study of pharmacology of T Aetiology or harm Ia A good recent systematic review Systematic review of cohort studies Does A cause disease D? Ib A rigorous study designed to answer the question A large well-designed cohort study Does drug D cause side effect S? II One or more prospective clinical studies A faulty cohort study III One or more retrospective clinical studies A case-control study IVa Formal expert consensus Delphi study of expert opinion IVb Other information Study of pathophysiology of D Diagnosis or prognosis Ia A good recent systematic review Systematic review of blind comparisons of T with gold standard Is T an accurate test for diagnosis Ib A rigorous study designed to answer the question Blind prospective comparison of T, F or M with gold standard for D or E of D? (eg, response to specific therapy) with multivariate analysis Is finding F an accurate predictor II One or more prospective clinical studies Analysis of prospective test results in patients enrolled in a randomised of event E? clinical trial of therapy for varying stages of D. Prospective validation study with univariate analysis Does severity measure M III One or more retrospective clinical studies Retrospective study of test results or findings in a database of patients accurately predict event E? with univariate or multivariate analysis IVa Formal expert consensus Delphi study of expert opinion about T IVb Other information Study of pathophysiology of D Public health, health policy Ia Economic and policy analysis based on good Economic and policy analysis with modelling and sensitivity analysis recent systematic reviews using data from systematic reviews of effectiveness and of cost studies in the same routine clinical settings Is policy P cost effective in the Ib Economic and policy analysis based on a rigorous Economic and policy analysis with modelling and sensitivity analysis NHS? study designed to answer the question using data from a randomised clinical trial of effectiveness and a cost study in the same routine clinical setting II Economic and policy analysis based on one or Economic and policy analysis with modelling and sensitivity analysis more prospective clinical studies using other prospective data in various settings III Economic and policy analysis based on one or Economic and policy analysis with modelling and sensitivity analysis more retrospective clinical studies using retrospective data IVa Formal expert consensus Delphi study of national expert opinion about P IVb Other information Local opinion about P http://thorax.bmj.com/ on October 1, 2021 by guest. Protected copyright. Appendix 4 Generic levels of evidence and guideline statement grades, appropriate across all types of clinical questions Evidence Guideline level Definition Example of study providing this level of evidence for a therapy question statement grade

Ia A good recent systematic review of studies designed to Cochrane systematic review of randomised controlled trials studying the A+ answer the question of interest effectiveness of flu vaccines Ib One or more rigorous studies designed to answer the Randomised controlled trial of effectiveness of a flu vaccine A2 question, but not formally combined II* One or more prospective clinical studies which illuminate, but Prospective cohort study comparing pneumonia rates in patients who are and B+ do not rigorously answer, the question are not vaccinated against flu; non-randomised controlled trial III{ One or more retrospective clinical studies which illuminate Audit or retrospective case control study, comparing flu vaccination history in B2 but do not rigorously answer the question patients who did and did not present with pneumonia IVa{ Formal combination of expert views Delphi study of UK expert recommendations for flu vaccination C IVb Other information Expert opinion, informal consensus; in vitro or in vivo studies on related topics D *Hard to differentiate Agency for Health Care Policy and Research’s ‘‘well designed controlled study without randomisation’’ (level IIa) from ‘‘other type of well-designed experimental study’’ (level IIb). {Major criterion is retrospective versus prospective data collection, since non-experimental designs are better suited than even randomised clinical trials for answering certain questions. {Distinguish formal consensus from informal consensus methods according to the Health Technology Assessment 1998 systematic review.

Thorax 2009;64(Suppl III):iii1–iii55. doi:10.1136/thx.2009.121434 iii55